Compositions for mucosal delivery of agents

ABSTRACT

Compositions and methods for mucosal delivery of agents are provided. The compositions are intended for administration to mucosal surface, such as oral, gastrointestinal and nasal mucosa. The compositions provided contain one or more mucoadhesive proteins and an agent to be delivered. Methods for delivery of agents using the compositions provided herein are also provided.

RELATED APPLICATIONS

This application is a continuation of allowed U.S. application Ser. No.11/155,262, entitled “COMPOSITIONS FOR MUCOSAL DELIVERY OF AGENTS,”filed Jun. 16, 2005 now U.S. Pat. No. 7,906,140, which claims priorityunder 35 U.S.C. §119(e) to U.S. provisional application Ser. No.60/580,877, entitled “COMPOSITIONS FOR MUCOSAL DELIVERY OF AGENTS” toBromley et al. filed Jun. 17, 2004. The subject matter of theseapplications is incorporated by reference herein.

This application is related to International PCT application No.PCT/US2005/021424, filed Jun. 16, 2005. The subject matter of PCTapplication No. PCT/US2005/021424 is incorporated by reference herein.

FIELD

Provided herein are pharmaceutical compositions for delivery of agents.Compositions formulated as emulsions for mucosal delivery are provided.

BACKGROUND

Numerous pharmaceutical substances are available for administration toanimals, including humans, for a variety of purposes. These substancesinclude, for example, therapeutic agents, such as drugs; dietarysupplements, such as vitamins; prophylactic agents, such as antigens foruse in vaccines; and diagnostic agents, such as labeled imaging agents.Administration of these substances can be via a number of routesincluding intramuscular, subcutaneous and oral administration.Intramuscular or subcutaneous administration of the substance suffersfrom disadvantages: relatively specialized skills are required toadminister the pharmaceutical; large scale administration can bedifficult to perform; it is expensive; and a number of side reactionscan occur to the substance administered. Many antibiotics (i.e.,tetracycline and penicillin), and hormones (i.e., progesterone andestrogen) can be administered successfully via the oral route.

There are, however, biologically active agents, for example certaindietary supplements, drugs, hormones and immunogens, whose efficacy isalmost totally lost upon oral administration. Included among thoseagents that cannot be effectively orally administered are polypeptideagents, such as Calcitonin, Erythropoetin, Granulocyte ColonyStimulating Factor, Stem Cell Factor, Granulocyte Colony StimulatingFactor, LHRH analogues, Somatostatin, Insulin, Interferons, PlasminogenActivator Inhibitors and species of DNA and RNA. Oral delivery ofcertain protein and polypeptide drugs is complicated by the presence ofproteolytic digestive enzymes in the stomach and intestines. Unprotectedproteins, which are administered orally, are largely degraded by suchenzymes before they are able to pass through the enteric wall and enterblood circulation. To some extent this effect can be overcome by theadministration of extremely large doses of the pharmaceutical agent.This approach, however, is not economically feasible for manypharmaceutical agents and may result in undesired side effects.

Thus, there continues to be a need for the development of compositionsand methods for convenient delivery of such substances to animals,including humans, efficiently. Accordingly, among the objectives herein,it is an objective to provide compositions and methods for convenientdelivery of agents to be delivered to a subject.

SUMMARY

Provided herein are compositions and methods for formulation of thecompositions for mucosal delivery and administration of agents toanimals, including humans. Provided are compositions and methods foradministering substances to animals, including humans, employing acarrier that facilitates entry of the substance to the mucosa in anon-specific manner.

The compositions provided herein are stable emulsions of oil in water orwater in oil, wherein an agent to be delivered is dissolved in eitherthe oil phase or the water phase. The emulsions are typically stabilizedby surface active molecules in the emulsion. The surfactant moleculesform various macro-molecular structures in an emulsion, such asmicelles, inverse micelles, lipid bilayers (liposomes) and cubosomes.The exact macromolecular structure formed depends on the relative sizesof the hydrophilic and hydrophobic regions of the surface activemolecule. The agent to be delivered can be distributed between thehydrophobic and hydrophilic phases of an oil-in-water or water-in-oiltype emulsion, or can be present predominantly in one of the phases. Incertain embodiments, the active agent in the emulsion is encapsulated ina delivery vehicle such as a micelle, a liposome or a cubosome or amixture thereof.

The compositions provided have a mucoadhesive property whereby thecomposition, when administered either orally or nasally, adheres toand/or anchors to a subject's mucous membrane for a period of timesufficient to quantitatively deliver the agent to be delivered to thesubject. The compositions contain a mucoadhesive substance that impartsthe composition a property of adhering or anchoring to a mucosalmembrane thereby effecting absorption of the agent through the mucosalmembrane. Typically, the mucoadhesive protein is present in an amountsufficient to confer mucoadhesive property to the composition. Suchmucosal absorption allows entry of the agent being delivered into thesystemic circulation without first passing through the liver, and thusalleviates the loss of activity upon passage through the liver.

The mucoadhesive substances for use herein include, but are not limitedto natural or synthetic proteins, polypeptides or fragments thereof thathave the property of adhering or penetrating into a mucus membrane for aperiod of time sufficient to achieve quantitative delivery of an agentto be delivered. In certain embodiments, the compositions are designedfor mucosal delivery of a therapeutically-effective amount of abiologically active agent to the subject. The mucoadhesive protein isgenerally dissolved in the water phase. In certain embodiments themucoadhesive protein can be dissolved in the oil phase. The mucoadhesiveprotein is typically anchored to polar head groups of the deliveryvehicles in the emulsion.

In certain embodiments, the compositions provided herein are formulatedto contact the mucosal membrane from about 5-24 hours or even longer, insome embodiments about 5, 10, 12, 14, 16, 18, 20, 22 or up to 24 hours.In some embodiments, the compositions provided herein are formulated tocontact the mucosal membrane from about 1 minute up to about 180, 120,100, 60, 40, 30, 20, 10, 5, 4, 3, or 2 minutes. In certain embodiments,the compositions provided herein are formulated to adhere or penetrateinto the mucosal membrane from about 5-24 hours or even longer, in someembodiments for about 5, 10, 12, 14, 16, 18, 20, 22 or up to 24 hours.In some embodiments, the compositions provided herein are formulated toadhere or penetrate into the mucosal membrane from about 1 minute up toabout 180, 120, 100, 60, 40, 30, 20, 10, 5, 4, 3, or 2 minutes. In otherembodiments, the compositions provided herein are formulated to adhereand penetrate into the mucosal membrane from about 5-24 hours or evenlonger, in some embodiments, for about 5, 10, 12, 14, 16, 18, 20, 22 orup to 24 hours. In some embodiments, the compositions provided hereinare formulated to adhere and penetrate into the mucosal membrane fromabout 1 minute up to about 180, 120, 100, 60, 40, 30, 20, 10, 5, 4, 3,or 2 minutes. In certain embodiments, the compositions provided hereinare formulated to adhere to the mucosal membrane from about 5-24 hoursor even longer, in some embodiments for about 5, 10, 12, 14, 16, 18, 20,22 or up to 24 hours. In some embodiments, the compositions providedherein are formulated to adhere to the mucosal membrane from about 1minute up to about 180, 120, 100, 60, 40, 30, 20, 10, 5, 4, 3, or 2minutes. In certain embodiments, the compositions provided herein areformulated to penetrate into the mucosal membrane from about 5-24 hoursor even longer, in some embodiments for about 5, 10, 12, 14, 16, 18, 20,22 or up to 24 hours. In some embodiments, the compositions areformulated to penetrate into the mucosal membrane from about 1 minute upto about 180, 120, 100, 60, 40, 30, 20, 10, 5, 4, 3, or 2 minutes.

Compositions provided herein can have a wide range of viscosities,typically in a range that assists retention of the composition on amucosal surface. Generally, the viscosity ranges from an oil likeviscosity, honey like viscosity, ketchup like viscosity, chocolate syruplike viscosity to peanut butter like or butter like viscosity. Theviscosity of the compositions can be measured by methods known to thoseof skill in the art, including measurement by using a viscometer such asBrookfield LVDV-I+ viscometer and T spindles with a heliopath adapter.The viscosity of the compositions provided can range from 10 cps, 100cps, 1000 cps, 10,000 cps, 100,000 cps, or 200,000 cps up to more than500,000 cps at 72° F.

The compositions provided herein are formulated to remain stable over arelatively long period of time. For example, the compositions providedherein are stored at room temperature, and remain stable for more than 1day, 1 week, 1 month and in certain embodiments up to more than 1 year.In certain embodiments, the compositions provided herein are deliveredto the oral mucosa or nasal mucosa. In certain embodiments, thecompositions are delivered to intestinal mucosa.

Also provided herein are methods of using the compositions. In certainembodiments, the methods provided herein are used for delivery of one ormore agents to be delivered including, but not limited to biologicallyactive agent such as minerals, vitamins, synthetic or natural compounds,pharmaceutical drugs, nutritional supplements, herbs, hormones, or thelike, which when introduced into the body cause a desired biologicalresponse, such as altering body function at the cellular, tissue ororgan level and/or altering cosmetic appearance. In certain embodiments,the methods are used to deliver a biological agent, wherein the agent isa drug or other pharmaceutical ingredient which suffers significant lossof activity in the lumen of the gastrointestinal tract or in the tissuesof the gastrointestinal tract during absorption process or upon passagethrough the liver after absorption in the intestinal tract.

In certain embodiments, the methods provided herein are useful fordelivery of therapeutics used in treatment of various disorders, such asneural disorders, respiratory disorders, immune system disorders,muscular disorders, reproductive disorders, gastrointestinal disorders,pulmonary disorders, digestive disorders, metabolic disorders,cardiovascular disorders, renal disorders, proliferative disorders,cancerous diseases and inflammation. The therapeutics delivered usingthe methods provided herein include, but are not limited toanticonvulsants, analgesics, antiparkinsons, anti-inflammatories,calcium antagonists, anesthetics, antimicrobials, antimalarials,antiparasitics, antihypertensives, antihistamines, antipyretics,alpha-adrenergic agonists, alpha-blockers, biocides, bactericides,bronchial dilators, beta-adrenergic blocking drugs, contraceptives,cardiovascular drugs, calcium channel inhibitors, depressants,diagnostics, diuretics, electrolytes, enzymes, hypnotics, hormones,hypoglycemics, hyperglycemics, muscle contractants, muscle relaxants,neoplastics, glycoproteins, nucleoproteins, lipoproteins, ophthalmics,psychic energizers, sedatives, steroids, sympathomimetics,parasympathomimetics, tranquilizers, urinary tract drugs, vaccines,vaginal drugs, vitamins, minerals, nonsteroidal anti-inflammatory drugs,angiotensin converting enzymes, polynucleotides, polypeptides,polysaccharides, and nutritional supplements including herbalsupplements. In certain embodiments, the methods are for delivery ofdietary supplements, including but not limited to vitamins, minerals,hormones and antioxidants.

Methods of making the compositions are also provided. The compositionsprovided herein are prepared by mixing an oil phase with a water phaseat a mixing speed that does not degrade and disintegrate any of theactive ingredients of the composition. The mixing speed can range fromabout 100 RPM up to about 60,000 RPM. The temperature, pressure, and pHconditions during the mixing step are maintained so that all thecomponents in the oil and water phase are dissolved and the activeingredients are not degraded in any way. A suitable temperature duringthe mixing step can be determined empirically for a particularcombination of ingredients in the composition. Typically, thetemperature is maintained at about 100-120° F., in some embodiments atabout 115° F. The pressure during the mixing is maintained at about 25PSI (pounds per square inch). The pH during the mixing step is afunction of the particular mucoadhesive protein and the agent to bedelivered in the composition. Typically the pH is basic or neutral.

The compositions can be prepared by mixing the water phase with an oilphase to form a water-in-oil emulsion. The agent to be delivered can bedissolved in the oil phase or in the water phase. Typically, amucoadhesive protein is present in the water phase in an amountsufficient to confer mucoadhesive property to the composition. Incertain embodiments, the compositions adhere or anchor to the mucosalsurface for an amount of time sufficient to achieve quantitativedelivery of the agent to be delivered. The compositions provided hereincan also include one or more surface active agent, and one or moreadditives, such as a polymer, a cosolvent, an antioxidant, anantiseptic, a buffering agent, a chelating agent, a colorant, aflavorant, an odorant, an osmotic modifier, a preservative, asolubilizer, a tonicifier, a trace element, a viscomodulator, or amixture thereof. Such additives are known to those of skill in the artand are described herein.

Articles of manufacture, containing packaging material for a compositionfor mucosal delivery and administration, a composition for mucosaldelivery of biologically active agents and a label that indicates thatthe composition is for achieving a desired biological response, such asaltering body function or altering cosmetic appearance. In certainembodiments, the articles of manufacture, contain a packaging material,a composition for mucosal delivery of biologically active agents and alabel that indicates that the composition is useful for treatment,prevention or amelioration of one or more symptoms of diseases ordisorders contemplated herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 indicates variance in blood glucose levels in a human afteradministration of a composition provided herein for 3 consecutive days.

DETAILED DESCRIPTION

A. Definitions

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as is commonly understood by one of skill in theart to which the invention(s) belong. All patents, patent applications,published applications and publications, Genbank sequences, websites andother published materials referred to throughout the entire disclosureherein, unless noted otherwise, are incorporated by reference in theirentirety. In the event that there are a plurality of definitions forterms herein, those in this section prevail. Where reference is made toa URL or other such identifier or address, it understood that suchidentifiers can change and particular information on the internet cancome and go, but equivalent information can be found by searching theinternet. Reference thereto evidences the availability and publicdissemination of such information.

As used herein, mucosa or mucus membrane refers to epithelial tissuethat lines the internal cavities of the body, such as oral cavity, therespiratory tract, the gastrointestinal tract, the lungs, and thegenitalia. The mucous membrane or mucosa protects the body from foreignmatter and pathogens and is permeable to a certain extent. Agentsdelivered through the mucosa enter circulation in hours or for as longas about 24 hours after administration (i.e. about 4-24 hours forinsulin). Entry of the agent to be delivered is a function of the drugand the mucoadhesive protein selected. The compositions provided hereinexploit the limited permeability of the mucosa and generally areformulated for delivery through the oral and nasal mucosa, although theycan be used formulated for delivery through any mucosal surface,including the mouth, nasal passages, gastrointestinal tract, lungs andthe mucosal layer of other tissues and organs.

As used herein, mucosal delivery refers to delivery of an agent in whichthe agent is introduced to the body across a mucous membrane whichallows for the avoidance of the gastrointestinal tract and first passliver metabolism and consequently allows the agent to directly enterinto circulation. This can include passage through the gastrointestinaltract as by oral ingestion, but refers to delivery through the muscosaof such locus.

As used herein, “contact to mucosal surface” refers to contact of thecomposition into the mucosal surface for an amount of time sufficient toachieve quantitative delivery of the composition. Contact of thecomposition can result in adhesion and/or penetration of the compositioninto the mucosal surface. The compositions provided herein can contactthe mucosal surface from 30 seconds up to about 24 hours. In certainembodiments, the composition contacts the mucosal surface for about 5,10, 12, 14, 16, 18, 20, 22 or up to 24 hours. In some embodiments, thecompositions provided herein contact the mucosal membrane from about 1minute up to about 180, 120, 100, 60, 40, 30, 20, 10, 5, 4, 3, or 2minutes.

As used herein, mucoadhesive property refers to a property whereby anatural or synthetic substance, such as a protein, when applied to amucosal epithelium adheres to or penetrates a subject's mucous membranefor a period of time sufficient to quantitatively deliver a compositionprovided herein to the subject. The composition can anchor in and/orpenetrate into a mucosal surface. Adhesion of mucoadhesives to a mucousmembrane occurs generally, although not necessarily or exclusively, viasecondary chemical bonds, such as hydrogen bonding and Van der Waalforces (Tabor et al., 1977 J. Colloid Interface Sci. 58:2 and Good 1977J. Colloid Interface Sci. 59:398). Parameters, such as mechanicalbinding to mucous membrane per se or the degree of biological effect ofan agent delivered can be used as a measurement parameter to detect andquantitate mucoadhesion.

As used herein, mucoadhesive compositions are viscous aqueous solutions.Their mucoadhesive (or penetrative) properties can be assessed bycomparison to a control composition that does not contain themucoadhesive protein(s) added to the mucoadhesvie composition. Atsimilar viscosities, the emulsion prepared with a mucoadhesive proteinor protein binds to a mucosal surface more strongly (i.e. more is boundor penetrates or is delivered) compared to a control emulsion withoutthe mucoadhesive protein or protein(s). Such increase in delivery orbinding or penetration is at least about 10%, 20%, 30%, 40%, 50%, 60%,70%, 80%, 90% or 100% greater mucosal binding than a control emulsion.

As used herein, mucoadhesive proteins refer to any natural or syntheticproteins, polypeptides or fragments thereof that possess themucoadhesive property. Non-limiting examples of mucoadhesive proteinsinclude mucin proteins and transferrins. In certain embodiments, theprotein for use in the compositions and methods provided herein islactoferrin. In certain embodiments, the mucoadhesive protein present ina composition provided herein is in an amount sufficient to confer amucoadhesive property to the composition.

As used herein, “biologically compatible substance” refers to asubstance which when administered to a subject, such as a human, doesnot produce undesired or toxic effects.

As used herein, “an agent,” is any substance that can be delivered viacompositions provided herein to a mucosal surface of a subject.

As used herein, “a biologically active agent,” “a biological agent,” or“an agent,” is any substance which when introduced into the body causesa desired biological response, such as altering body function at thecellular, tissue or organ level and/or altering cosmetic appearance.Such substance can be any synthetic or natural element or compound,protein, cell, or tissue including a pharmaceutical, drug, therapeutic,nutritional supplement, herb, hormone, or the like, or any combinationsthereof. The terms also encompass pharmaceutically acceptable,pharmacologically active derivatives of those active agents specificallymentioned herein, including, but not limited to, salts, esters, amides,prodrugs, active metabolites, isomers, fragments, analogs, and the like.When the terms “biologically active agent,” “biological agent” and“agent” are used, then, or when a particular active agent isspecifically identified, it is intended to include the active agent perse as well as pharmaceutically acceptable, pharmacologically activesalts, esters, amides, prodrugs, active metabolites, isomers, fragmentsand analogs.

As used herein, a subject is defined as an animal, including a mammal,typically a human.

As used herein, quantitative delivery refers to delivery of asubstantial portion of the amount administered, and is typically,greater than 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,97%, 98%, or 99%.

As used herein, therapeutically effective amount refers to an amount ofthe active agent for a desired therapeutic, prophylactic, or otherbiological effect or response when a composition is administered to asubject in a single dosage form. The particular amount of active agentin a dosage will vary widely according to conditions such as the natureof the active agent, the nature of the condition being treated, the ageand size of the subject.

As used herein, an emulsion is defined as a colloidal dispersion of twoimmiscible liquids, such as oil and water, in the form of droplets. Theemulsions are generally stabilized by an interfacial film of surfaceactive agents or surfactant molecules, such as polysorbate −80 and thestability of an emulsion can be determined by well known routinemethods.

As used herein, surfactants (or “surface-active agents”) are chemical ornaturally occurring entities which, when dissolved in an aqueoussolution, reduce the surface tension of the solution or the interfacialtension between the aqueous phase and the oil phase, to form a stableoil in water or water in oil emulsion. The surfactant molecules areamphiphilic and contain hydrophilic head groups and hydrophobic tails.The surfactant molecules form various macro-molecular structures in anemulsion, such as micelles, inverse micelles, lipid bilayers (liposomes)and cubosomes. The exact macromolecular structure which is formeddepends on the relative sizes of the hydrophilic and hydrophobic regionsof the surface active molecules.

Micelle formation is favored when the cross sectional area of thehydrophilic region of the surface active molecule is greater than thatof the hydrophobic part of the molecule. For example, sodium palmitatecontains a hydrocarbon chain (the hydrophobic portion of the molecule)and an ionic base (the hydrophilic portion of the molecule), and acts asan emulsifying agent that binds water and oil phases. That is, it allowsoil and water to be broken into tiny droplets suspended or dispersed inwater as spherical micelles, wherein the hydrophilic head groups arrangeat the periphery of the sphere and hydrophobic tails are at the center.

When the cross sectional area of the hydrophobic region of the moleculeis greater than that of the hydrophilic part of the molecule, theformation of hexagonal phase structures, sometimes referred to as aninverse micelle is favored, e.g., dimyristoyl-phosphatidylethanolamine(DMPE).

For surface active molecules in which the cross sectional area of thehydrophilic region of the molecule is slightly less than, or equal to,that of the hydrophobic part of the molecule, such as many phospholipids(which are amphipathic type of lipids that contain phosphate, that is,molecules containing one phosphate, a glycerol and one or more fattyacids), the formation of bilayers is favored, e.g.,dipalmitoylphosphatidylcholine (DPPC). These bilayers are twodimensional sheets in which all of the hydrophobic portions, e.g., acylside chains, are shielded from interaction with water except those atthe ends of the sheet. An energetically unfavorable interaction of theacyl chains with water results in the folding of the bilayers to formthree-dimensional vesicles. These vesicles are referred to as“liposomes.” Liposomes may be formed as a single bilayer enclosing asingle aqueous space (small unilamellar vesicles; SUVS) or may becomposed of concentric bilayers with many aqueous spaces alternatingwith the bilayers (multilamellar vesicles; MLVS). Liposomes can be usedto encapsulate both hydrophobic and hydrophilic active agents.Hydrophobic active agents are typically partitioned within the bilayerswhereas hydrophilic active agents are typically trapped within theaqueous compartments. The advantages of using liposomes as acarrier/encapsulation system is that they are stable and can protect theactive agents from degradation, e.g., by oxygen, digestive enzymes, etc.

As used herein, a “delivery vehicle” refers to macro-molecularstructures in an emulsion, such as micelles, inverse micelles, lipidbilayers (liposomes) and cubosomes or a mixture thereof.

As used herein, “protein is associated with a delivery vehicle” meansthe mucoadhesive protein is associated with a delivery vehicle viachemical or physical interaction, such as hydrogen bond or van derwaal's forces. The mucoadhesive protein, such as lactoferrin can be forexample, associated with the polar head groups of the delivery vehicles,such as micelles via a chemical interaction, such as a hydrogen bond.

As used herein, “agent is associated with a delivery vehicle” means thedelivery vehicle contains the agent to be delivered. The agent can befor example, encapsulated in a micelle or encapsulated in the liposomebilayers.

As used herein, viscosity refers to a physical property of fluids thatdetermines the internal resistance to shear forces and is expressed incentipoise (cp).

The oil phase in the emulsion provided herein can be any nontoxic oil,biocompatible oil, which includes, but is not limited to mono-, di- andtriglycerides, fatty acids and their esters, ethers and esters ofpropylene glycol or other polyols. The fatty acids and esters (used assuch or where they form part of a glyceride) can be short chain, mediumchain or long chain. As used herein, medium chain represents ahydrocarbon chain of C₈ to C₁₂ and short chain is a hydrocarbon chain ofless than C₈ and long chain means a hydrocarbon chain of more than C₁₂.The water phase in the emulsion can be water, aqueous solutions,alcohols, alcohol solutions, and the like.

As used herein, the stability of a composition provided herein refers tothe length of time at a given temperature that greater than 10%, 20%,30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,97%, 98% or 99% of the initial amount of the agent to be delivered,e.g., insulin, is present in the composition. Thus, for example, acomposition that is stable for 30 days at 25° C. would have greater than10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90% 91%, 92%, 93%, 94%,95%, 96%, 97%, 98% or 99% of the initial amount of active ingredientpresent in the composition at 30 days following storage at 25° C.

As used herein, pharmaceutically acceptable derivatives of a compoundinclude salts, esters, enol ethers, enol esters, acids, bases, solvates,hydrates or prodrugs thereof. Such derivatives can be readily preparedby those of skill in this art using known methods for suchderivatization. The compounds produced can be administered to animals orhumans without substantial toxic effects and either are pharmaceuticallyactive or are prodrugs. Pharmaceutically acceptable salts include, butare not limited to, amine salts, such as but not limited toN,N′-dibenzylethylenediamine, chloroprocaine, choline, ammonia,diethanolamine and other hydroxyalkylamines, ethylenediamine,N-methylglucamine, procaine, N-benzylphenethylamine,1-para-chlorobenzyl-2-pyrrolidin-1′-ylmethylbenzimidazole, diethylamineand other alkylamines, piperazine and tris(hydroxymethyl)aminomethane;alkali metal salts, such as but not limited to lithium, potassium andsodium; alkali earth metal salts, such as but not limited to barium,calcium and magnesium; transition metal salts, such as but not limitedto zinc; and other metal salts, such as but not limited to sodiumhydrogen phosphate and disodium phosphate; and also including, but notlimited to, salts of mineral acids, such as but not limited tohydrochlorides and sulfates; and salts of organic acids, such as but notlimited to acetates, lactates, malates, tartrates, citrates, ascorbates,succinates, butyrates, valerates and fumarates. Pharmaceuticallyacceptable esters include, but are not limited to, alkyl, alkenyl,alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkyl andheterocyclyl esters of acidic groups, including, but not limited to,carboxylic acids, phosphoric acids, phosphinic acids, sulfonic acids,sulfinic acids and boronic acids.

Pharmaceutically acceptable solvates and hydrates are complexes of acompound with one or more solvent or water molecule, in certainembodiments 1 to about 100, in other embodiments 1 to about 10, infurther embodiments one to about 2, 3 or 4, solvent or water molecules.

As used herein, treatment means any manner in which one or more of thesymptoms of a condition, disorder or disease are ameliorated orotherwise beneficially altered. Treatment also encompasses anypharmaceutical use of the compositions herein, such as use for treatingdiabetes.

As used herein, amelioration of the symptoms of a particular disorder byadministration of a particular pharmaceutical composition refers to anylessening, whether permanent or temporary, lasting or transient that canbe attributed to or associated with administration of the composition.

As used herein, a prodrug is a compound that, upon in vivoadministration, is metabolized or otherwise converted to thebiologically, pharmaceutically or therapeutically active form of thecompound. To produce a prodrug, the pharmaceutically active compound ismodified such that the active compound will be regenerated by metabolicprocesses. The prodrug can be designed to alter the metabolic stabilityor the transport characteristics of a drug, to mask side effects ortoxicity, to improve the flavor of a drug or to alter othercharacteristics or properties of a drug. By virtue of knowledge ofpharmacodynamic processes and drug metabolism in vivo, those of skill inthis art, once a pharmaceutically active compound is known, can designprodrugs of the compound (see, e.g., Nogrady (1985) Medicinal ChemistryA Biochemical Approach, Oxford University Press, New York, pages388-392).

It is to be understood that the compounds for use in the compositionsand methods provided herein can contain chiral centers. Such chiralcenters may be of either the (R) or (S) configuration, or may be amixture thereof. Thus, the compounds for use in the compositionsprovided herein may be enantiomerically pure, or be stereoisomeric ordiastereomeric mixtures. It is to be understood that the chiral centersof the compounds provided herein may undergo epimerization in vivo.Thus, one of skill in the art will recognize that administration of acompound in its (R) form is equivalent, for compounds that undergoepimerization in vivo, to administration of the compound in its (S)form.

B. Compositions

1. Mucosal Delivery

Provided herein are compositions and methods for mucosal delivery ofagents, particularly agents that are normally difficult to administer orineffective when administered orally or nasally. The compositionsprovided herein contain one or more mucoadhesive proteins that impart amucoadhesive property to the composition. Contacting a mucosal surfacein a subject with a composition results in delivery of composition,including active and inactive components into circulation. Thecompositions provided herein are for delivery of agents, such asbiologically active agents, through mucosa, such as oral, nasal orintestinal mucosa.

Mucosal delivery systems offer benefits over other methods of delivery.For example, absorption through the mucous membrane leads the deliveredactive agent directly into the circulatory system. This allows suchagents, in certain embodiments, to bypass the gastrointestinal tract aswell as first pass liver metabolism. Secondly, the biologically activeagents such as drugs directly enter the circulatory system, which allowsthe therapeutic to be rapidly transported to the site of need. Thefaster the drug reaches its target area, the faster it can begin toelicit its desired effect. Further, the avoidance of thegastrointestinal tract and first pass metabolism means that much less ofthe drug can be administered to achieve the same effect, allowing forlower dosages to be administered and fewer side effects.

Some common modes of mucosal administration include oral and nasaladministrations. Those of skill in the art are familiar with a varietyof modes of administration (see, e.g., Almeida et al. Journal of DrugTargeting 3, 456-467 (1996), which provides a review of mucosaladministration of vaccines in general, and nasal administration ofvaccines in particular). The compositions upon contacting with themucosal surface, adhere thereto or penetrate through the mucosalsurface, for an amount of time sufficient to achieve quantitativedelivery of the composition, including, but not limited to less than 1minute up to more than 3 hours. Various parameters known in the art canbe used for measurement of mucoadhesion. Such parameters include, butare not limited to, mechanical binding to mucous membrane per se or thedegree of biological effect of an agent delivered. The compositions areformulated to adhere to or penetrate into the mucosal surface for about1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120,150 minutes or up to more than 180 minutes after being delivered to themucosa. In certain embodiments, compositions are formulated to adhere toor penetrate into the mucosal surface for about 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 12, 14, 16, 18, 20, 22, 24 or more hours.

Mucosal delivery of agents can be effected either in the absence or inthe presence of a carrier. Mucosal administration in the presence of acarrier serves various purposes, such as controlled release ofbiologically active molecules, targeting of biologically activemolecules to specific tissues, and facilitating penetration into themucosal layer.

2. Compositions

The compositions provided herein, which provide mucosal delivery ofagents, are formulated as emulsions, including oil in water and water inoil emulsions. In preparing the compositions, an agent to be deliveredis dissolved either in the oil phase or the water phase prior to formingan emulsion. The compositions optionally include additional ingredients,such as surface active agents for stabilizing the emulsions.

Compositions provided herein can have a wide range of viscosities,typically ranging from about 10 cps; 50 cps; 100 cps; 300 cps; 500 cps;750 cps; 1000 cps; 3000 cps; 6000 cps; 8000 cps; 10,000 cps; 20,000 cps;30,000 cps; 40,000 cps; 50,000 cps; 60,000 cps; 70,000 cps; 80,000 cps;90,000 cps; 100,000 cps; 150,000 cps; 200,000 cps; 130,000 cps; 250,000cps; or 280,000 cps up to more than 500,000 cps at 72° F. The viscosityof the compositions can be measured by methods known to those of skillin the art, including measurement by using a viscometer such asBrookfield LVDV-I+ viscometer and T spindles with a heliopath adapter.

In the compositions provided herein, oil phase, aqueous phase andemulsifier can be used in a wide range of ratios to make the emulsions.The oil-in-water emulsions contain at least 25% of water by weight, inone embodiment between 30% and 80% and in another embodiment between 40%and 95%. The oil phase in the oil in water emulsions is at least 1%, 2%,3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30% or more by weight ofthe emulsion. The emulsifier or surfactant in the emulsions is at least0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, or 25% byweight of the emulsion.

The water-in-oil emulsions contain at least 25% of oil by weight, in oneembodiment between 30% and 80% and in another embodiment between 40% and95% of oil by weight. The water phase in the water in oil emulsions isat least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30% ormore by weight of the emulsion. The emulsifier or surfactant in theemulsions is at least 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%,15%, 20%, or 25% by weight of the emulsion.

The compositions provided herein also can include one or more otheradditives, such as a polymer, a cosolvent, an antioxidant, anantiseptic, a buffering agent, a chelating agent, a colorant, aflavorant, an odorant, an osmotic modifier, a preservative, asolubilizer, a tonicifier, a trace element, a viscomodulator and amixture thereof. Such additional additives can be present in the oilphase, the aqueous phase, or both.

a. Mucoadhesive Proteins

The compositions contain one or more mucoadhesive proteins. Themucoadhesive proteins for use in the compositions and methods providedherein include any protein that imparts a mucoadhesive property to thecomposition whereby the composition when administered to a subject'smucosal surface, such as oral or nasal mucosa, adheres or penetratesinto the mucosal epithelium of the subject for a period of timesufficient to achieve quantitative delivery of an agent to be delivered.In certain embodiments, the compositions adhere to or penetrate throughthe mucosal membrane for a period of time sufficient to locally delivera therapeutically-effective amount of an active agent in thecomposition. Adhesion of mucoadhesive protein to the mucous membraneoccurs primarily via secondary chemical bonds, such as hydrogen bondingand Van der Waal forces.

Any mucoadhesive protein that is biologically compatible can beemployed. Mucoadhesive proteins for use herein include, but are notlimited to natural or synthetic proteins, polypeptides or fragmentsthereof that possess the mucoadhesive property. Mucoadhesive proteinscan be screened for their ability to be used as mucoadhesives formucosal delivery of compositions provided herein according to themethodology described in Smart et al., 1982 J. Pharm. Pharmacol. 34:70 Pand Smart et al., 1984 J. Pharm. Pharmacol. 36:295. The methodologyinvolves estimating values of adhesive strength between the mucoadhesiveprotein and the mucous membrane.

In certain embodiments, the mucoadhesive proteins are selected from afamily of mucin proteins and transferrins. In certain embodiments, themucoadhesive protein is from the transferrin family and is selected frombovine lactoferrin, human lactoferrin, lactoferrin binding proteins,recombinant human lactoferrin, lactoferricin, lactoferricin b,transferrin binding proteins, bovine transferrin, ovotransferrin,neutrophil granules, apo-lactoferrin and lanthanide-lactoferrin. Incertain embodiments, the mucoadhesive proteins are selected from amonglactoferrin, lactoferrin binding proteins, recombinant lactoferrin,lactoferricin, lactoferricin b, transferrin binding proteins,transferrin, ovotransferrin, neutrophil granules, apo-lactoferrin,immunoglobulin, albumin and lanthanide-lactoferrin. In certainembodiments, the mucoadhesive protein is selected from albumin,immunoglobulin and lactoferrin.

In certain embodiments, the mucoadhesive protein for use in thecompositions and methods provided herein is lactoferrin. In certainembodiments, the compositions contain one, two or three mucoadhesiveproteins. In certain embodiments, the compositions contain onemucoadhesive protein. In certain embodiments, the mucoadhesive proteinin the compositions provided herein is present in an amount sufficientto confer a mucoadhesive property to the composition.

The mucoadhesive proteins can associate with the delivery vehicle viachemical or physical interaction. For example, the mucoadhesive proteincan be hydrogen bonded with polar head groups of the micelles or theliposomes or other vehicles that are present in the emulsion in thecompositions provided herein. Such compositions when administered eitherorally or nasally, to a subject in need thereof, adhere to or penetratethrough the mucosal membrane via chemical or physical bond, such assecondary chemical bonds, including hydrogen bonding and Van der Waalforces, thereby providing sustained or prolonged coating of thecomposition on the epithelium of the oral cavity or nasal cavitydepending on the mode of administration. The sustained coating of thecomposition allows for increased contact time between the compositionand the epithelial layer, which in turn results in enhanced absorptionof the active agent in to the mucosal layer.

The amount of mucoadhesive protein in the compositions provided herein,is an amount that results in quantitative delivery of an agentformulated therewith. The amount to be added can vary depending upon theagent delivered and other components of a composition, but it can bedetermined empirically by formulating compositions and testing them fordelivery using any suitable assay known to those of skill in the art oras described herein.

Typically, the mucoadhesive protein is present at a concentration ofabout 0.05% by weight up to about 80%, generally 0.1, 0.2, 0.3, 0.4,0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, or 40% by weight upto about 50% by weight, of the total weight of the composition. In otherembodiments, the mucoadhesive protein is present at a concentration ofabout 0.1% by weight up to about 30% by weight of the total weight ofthe composition. In other embodiments, the mucoadhesive protein ispresent at a concentration of about 0.1% by weight up to about 20% byweight of the total weight of the composition. In other embodiments, themucoadhesive protein is present at a concentration of about 0.05% byweight up to about 15% by weight of the total weight of the composition.In other embodiments, the mucoadhesive protein is present at aconcentration of about 0.05% by weight up to about 12% by weight of thetotal weight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 0.05% by weight up toabout 10% by weight of the total weight of the composition. In otherembodiments, the mucoadhesive protein is present at a concentration ofabout 0.05% by weight up to about 8% by weight of the total weight ofthe composition. In other embodiments, the mucoadhesive protein ispresent at a concentration of about 0.05% by weight up to about 5% byweight of the total weight of the composition. In other embodiments, themucoadhesive protein is present at a concentration of about 8% by weightup to about 10% by weight of the total weight of the composition. Inother embodiments, the mucoadhesive protein is present at aconcentration of about 9% by weight up to about 10% by weight of thetotal weight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 15% by weight of thetotal weight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 12% by weight of thetotal weight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 10% by weight of thetotal weight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 9.5% by weight of thetotal weight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 9% by weight of the totalweight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 8% by weight of the totalweight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 6% by weight of the totalweight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 4% by weight of the totalweight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 2% by weight of the totalweight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 1% by weight of the totalweight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 0.8% by weight of thetotal weight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 0.6% by weight of thetotal weight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 0.4% by weight of thetotal weight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 0.1% by weight of thetotal weight of the composition. In other embodiments, the mucoadhesiveprotein is present at a concentration of about 0.05% by weight of thetotal weight of the composition.

b. Oils

The oils for use in the compositions include any oil obtained from anatural or synthetic source that is suitable for consumption by asubject. Oils suitable for administration to subjects, including humans,are known. Any such oil can be used. The oil can be of vegetable oranimal origin. The oil phase also can be synthetic or semisynthetic oilsthat are nontoxic to a subject. Exemplary of oils for use hereininclude, but are not limited to mono-, di- and triglycerides, fattyacids, such as oleic, linoleic, palmitic, stearic, conjugated formsthereof and their esters, ethers and esters of propylene glycol or otherpolyols. In certain embodiments, the oils are short, medium or longchain triglycerides. In certain embodiments, the oils are medium chaintriglycerides (MCT5). In certain embodiments, the MCT is tricaprylictriglyceride ester (also known as Neobee® M5). Exemplary sources foroils contemplated herein include, but are not limited to All Spice,Almond, Anise, Apple, Apricot, Avocado, Basil, Bayberry, Benzoin,Bergamot, Borage Seed, Cajeput, Calendula, Canola, Carnation, Carrotseed, Cassia bark, Castor, Cayenne, Cedarwood, Chamomile, Cinnamon,Citronella, Conjugated Linolenic Acid, Clary sage, Clove bud, Coconut,Cod Liver, Corn, Cranberry, Cypress, Evening Primrose, Eucalyptus,Evergreen, Fir, Fish 18:12, Flax Seed, Frangipani, Frankincense,Freesia, Gardenia, Ginger, Grape Seed, Grapefruit, Heather, Honeysuckle,Hyacinth, Jasmine, Jojoba, Juniper berry, Lavender, Lecithin, Lemon,Lemon balm, Lemon, verbena, Lemongrass, Lilac, Lily of the valley, Lime,Magnolia, MCT, Menthol, Mulberry, Musk, Myrrh Oat, Olive, Orange,Oregano, Palm, Patchouli, Peach, Pennyroyal, Peppermint, Petitgrain,Pine, Pumpkin Seed, Rice Bran, Rose, Rosemary, Rosewood, Safflower,Sage, Salmon, Sandalwood, Sesame, Shark Liver, Soy Bean, Spearmint,Squalene, Strawberry, Sunflower, Tangerine, Tea tree, Thuja (Cedarleaf), Thyme, Tuna, Vanilla, Vitamin E, Wheat Germ, Wintergreen andYlang ylang. In certain embodiments, the oil phase contains oat oil andtri caprylic triglyceride ester (also known as Neobee® M5).

The oil is present in an amount sufficient to dissolve the oil solubleingredients in the composition. The amount generally is a function ofthe locus of administration, the agent to be administered and other suchparameters and can be empirically determined. For example, in someembodiments, the oil is present at a concentration of about 1%, 2%, 3%,4%, 5%, 10%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%,80%, 85%, 90%, 95% or more by weight. Thus, in certain embodiments, theoil is present at about 3, 4, or 5% by weight up to about 90% by weightof the total weight of the composition. In other embodiments, the oil ispresent at a concentration of about 3, 4, or 5% by weight up to about85% by weight of the total weight of the composition. In otherembodiments, the oil is present at a concentration of about 5% by weightup to about 70% by weight of the total weight of the composition. Inother embodiments, the oil is present at a concentration of about 5% byweight up to about 50% by weight of the total weight of the composition.In other embodiments, the oil is present at a concentration of about 5%by weight up to about 45% by weight of the total weight of thecomposition. In other embodiments, the oil is present at a concentrationof about 5% by weight up to about 40% by weight of the total weight ofthe composition. In other embodiments, the oil is present at aconcentration of about 5% by weight up to about 35% by weight of thetotal weight of the composition. In other embodiments, the oil ispresent at a concentration of about 5% by weight up to about 30% byweight of the total weight of the composition. In other embodiments, theoil is present at a concentration of about 5% by weight up to about 20%by weight of the total weight of the composition. In other embodiments,the oil is present at a concentration of about 45% by weight of thetotal weight of the composition. In other embodiments, the oil ispresent at a concentration of about 40% by weight of the total weight ofthe composition. In other embodiments, the oil is present at aconcentration of about 35% by weight of the total weight of thecomposition. In other embodiments, the oil is present at a concentrationof about 30% by weight of the total weight of the composition. In otherembodiments, the oil is present at a concentration of about 20% byweight of the total weight of the composition. In other embodiments, theoil is present at a concentration of about 10% by weight of the totalweight of the composition. In other embodiments, the oil is present at aconcentration of about 7% by weight of the total weight of thecomposition. In other embodiments, the oil is present at a concentrationof about 5% by weight of the total weight of the composition.

c. Surface Active Agents

The compositions provided herein can contain one or more surface activeagents that are added in an amount sufficient to form a stable emulsion.The appropriate amount of surface active agent is a function of theagent for delivery and other components present in the emulsion, sincesome agents can have self-emulsifying properties and other agents andcomponents affect surface tension.

The surface active agents for use herein are substances which, whendissolved in an aqueous solution, reduce the surface tension of thesolution or the interfacial tension between the aqueous phase and theoil phase, to form a stable oil in water or water in oil emulsion. Thesurfactant molecules are amphiphilic and contain hydrophilic head groupsand hydrophobic tails. The surfactant molecules form variousmacro-molecular structures in an emulsion, such as micelles, inversemicelles, lipid bilayers (liposomes) and cubosomes. The exactmacromolecular structure which is formed depends on the relative sizesof the hydrophilic and hydrophobic regions of the surface activemolecule. In certain embodiments, the surface active agent is selectedfrom sodium lauryl sulfate; sorbitan laurate, sorbitan palmitate,sorbitan stearate (available under the tradename Span® 20, 40, 60 etc.);polysorbates such as polyoxyethylene (20) sorbitan monolaurate,polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20)sorbitan monostearate (available under the tradename TWEENS® 20, 40, 60etc.); benzalkonium chloride, mixed chain phospholipids, cationiclipids, oligolipids, phospholipids, carnitines, sphingosines,sphingomyelins, ceramides, glycolipids, lipoproteins, apoproteins,amphiphilic proteins, amphiphilic peptides, amphiphilic syntheticpolymers, and combinations thereof. Other exemplary surface activeagents for use herein include, but are not limited to:

i) Natural lipids, i.e. Cholesterol, Sphingosine and Derivatives,Gangliosides, Sphingosine derivatives (Soy Bean), Phytosphingosine andderivatives (Yeast), Choline (Phosphatidylcholine), Ethanolamine(Phosphatidylethanolamine), Glycerol (Phosphatidyl-DL-glycerol),Inositol (Phosphatidylinositol), Serine (Phosphatidylserine (SodiumSalt)), Cardiolipin, Phosphatidic Acid, Egg Derived, Lyso (Mono Acyl)Derivatives (Lysophosphatides), Hydrogenated Phospholipids, Lipid TissueExtracts,

ii) Synthetic lipids, i.e. Asymmetric Fatty Acid, Symmetric FattyAcid—Saturated Series, Symmetric Fatty Acid—Unsaturated Series, AcylCoenzyme A (Acetoyl Coenzyme A, Butanoyl Coenzyme A, Crotanoyl CoenzymeA, Hexanoyl Coenzyme A, Octanoyl Coenzyme A, Decanoyl Coenzyme A,Lauroyl Coenzyme A, Myristoyl Coenzyme A, Palmitoyl Coenzyme A, StearoylCoenzyme A, Oleoyl Coenzyme A, Arachidoyl Coenzyme A, ArachidonoylCoenzyme A, Behenoyl Coenzyme A, Tricosanoyl Coenzyme A, LignoceroylCoenzyme A, Nervonoyl Coenzyme A, Hexacosanoyl Coenzyme A,

iii) Sphingolipids, i.e. D-erythro (C-18) Derivatives (Sphingosine, suchas: D-erythro Sphingosine (synthetic), Sphingosine-1-Phosphate, N,NDimethylsphingosine, N,N,N-Trimethylsphingosine,Sphingosylphosphorylcholine, Sphingomyelin and GlycosylatedSphingosine), Ceramide Derivatives (Ceramides, D-erythroCeramide-1-Phosphate, Glycosulated Ceramides), Sphinganine(Dihydrosphingosine) (Sphinganine-1-Phosphate, Sphinganine (C20),D-erythro Sphinganine, N-Acyl-Sphinganine C2, N-Acyl-Sphinganine C8,N-acyl-Sphinganine C16, N-Acyl-Sphinganine C18, N-Acyl-Sphinganine C24,N-Acyl-Sphinganine C24:1), Glycosylated (C18) Sphingosine andPhospholipid Derivatives (Glycosylated-Sphingosine) (Sphingosine,βD-Glucosyl, Sphingosine, βD-Galactosyl, Sphingosine, βD-Lactosyl),Glycosylated-Ceramide (D-Glucosyl-β1-1′Ceramide (C8),D-Galactosyl-β1-1′Ceramide (C8), D-Lactosyl-β1-1′Ceramide (C8),D-Glucosyl-β1-1′Ceramide (C12), D-Galactosyl-β1-1′Ceramide (C12),D-Lactosyl-β1-1′Ceramide (C12)), Glycosylated—Phosphatidylethanolamine(1,2-Dioleoyl-sn-Glycero-3-Phosphoethanolamine-N-Lactose), D-erythro(C17) Derivatives (D-erythro Sphingosine, D-erythroSphingosine-1-phosphate), D-erythro (C20) Derivatives (D-erythroSphingosine), L-threo (C18) Derivatives (L-threo Sphingosine, Safingol(L-threo Dihydrosphingosine)), Sphingosine Derivatives (Egg, Brain &Milk) (D-erythro-Sphingosine, Sphingomyelin, Ceramides, Cerebrosides,Brain Sulfatides), Gangliosides (Gangliosides Structures,Gangliosides—Ovine Brain, Gangliosides—Porcine Brain), SphingosineDerivatives (Soy Bean) (Glucosylceramide), Phytosphingosine Derivatives(Yeast) (Phytosphingosine, D-ribo-Phytosphingosine-1-Phosphate, N-AcylPhytosphingosine C2, N-Acyl Phytosphingosine C8, N-Acyl PhytosphingosineC18,

iv) Acyl coenzyme A, i.e. Acetoyl Coenzyme A (Ammonium Salt), ButanoylCoenzyme A (Ammonium Salt), Crotanoyl Coenzyme A (Ammonium Salt),Hexanoyl Coenzyme A (Ammonium Salt), Octanoyl Coenzyme A (AmmoniumSalt), Decanoyl Coenzyme A (Ammonium Salt), Lauroyl Coenzyme A (AmmoniumSalt), Myristoyl Coenzyme A (Ammonium Salt), Palmitoyl Coenzyme A(Ammonium Salt), Stearoyl Coenzyme A (Ammonium Salt), Oleoyl Coenzyme A(Ammonium Salt), Arachidoyl Coenzyme A (Ammonium Salt), ArachidonoylCoenzyme A (Ammonium Salt), Behenoyl Coenzyme A (Ammonium Salt),Tricosanoyl Coenzyme A (Ammonium Salt), Lignoceroyl Coenzyme A (AmmoniumSalt), Nervonoyl Coenzyme A (Ammonium Salt), Hexacosanoyl Coenzyme A(Ammonium Salt), Docosahexaenoyl Coenzyme A (Ammonium Salt),

v) Oxidized lipids, i.e.1-Palmitoyl-2-Azelaoyl-sn-Glycero-3-Phosphocholine,1-O-Hexadecyl-2-Azelaoyl-sn-Glycero-3-Phosphocholine,1-Palmitoyl-2-Glutaroyl-sn-Glycero-3-Phosphocholine (PGPC),1-Palmitoyl-2-(9′-oxo-Nonanoyl)-sn-Glycero-3-Phosphocholine,1-Palmitoyl-2-(5′-oxo-Valeroyl)-sn-Glycero-3-Phosphocholine,

vi) Ether lipids, i.e.: Diether Lipids (Dialkyl Phosphatidylcholine,Diphytanyl Ether Lipids), Alkyl Phosphocholine (Dodedylphosphocholine),O-Alkyl diacylphosphatidylcholinium(1,2-Diacyl-sn-Glycero-3-Ethylphosphocholine), Synthetic PAF &Derivatives (1-Alkyl-2-Acyl-Glycero-3-Phosphocholine & Derivatives),

vii) Fluorescent lipids, i.e.: Glycerol Based (Phosphatidylcholine(NBD), Phosphatidic Acid (NBD), Phosphatidylethanolamine (NBD),Phosphatidylglycerol (NBD), Phosphatidylserine (NBD)), Sphingosine Based(Ceramide (NBD), Sphingomyelin (NBD), Phytosphingosine (NBD), GalactosylCerebroside (NBD)), Headgroup Labeled Lipids (Glycerol Based)(Phosphatidylethanolamine (NBD), Phosphatidylethanolamine (LissamineRhodamine B), Dioleoyl Phosphatidylethanolamine (Dansyl, Pyrene,Fluorescein), Phosphatidylserine (NBD), Phosphatidylserine (Dansyl)),25-NBD-Cholesterol,

viii) Other lipids including, but not limited to Lecithin, Ultralec-P(ADM), Soy powder,

ix) Surfactants including, but not limited to polyethylene glycol 400;sodium lauryl sulfate; sorbitan laurate, sorbitan palmitate, sorbitanstearate (available under the tradename Span® 20-40-60 etc.);polysorbates such as polyoxyethylene (20) sorbitan monolaurate,polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20)sorbitan monostearate (available under the tradename TWEENS® 20-40-60etc.); benzalkonium chloride.

In certain embodiments, the phospholipids for use arephosphatidylcholines, phosphatidylethanolamines, phosphatidylserines,phosphatidylglycerols, phosphatidylinositols, phosphatidic acids, mixedchain phospholipids, lysophospholipids, hydrogenated phospholipids,partially hydrogenated phospholipids, and mixtures thereof.

In certain embodiments, the surface active agent is selected frompolysorbate-80, lecithin and phosphatidylcholine. The surface activeagents are present in an amount sufficient to form a stable emulsion.

The amount of surface active agent can be empirically determined and isa function of the agent selected and the desired form of the resultingcomposition. The amount include can be from less than 0.1% by weight upto 35% or more. In certain embodiments, the surface active agent ispresent at a concentration of about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%,10%, 15%, 20% or 25% by weight up to about 30% by weight of the totalweight of the composition. In certain embodiments, the surface activeagent is present at a concentration of about 1% by weight up to about20% by weight of the total weight of the composition. In certainembodiments, the surface active agent is present at a concentration ofabout 1% by weight up to about 15% by weight of the total weight of thecomposition. In other embodiments, the surface active agent is presentat a concentration of about 1% by weight up to about 10% by weight ofthe total weight of the composition. In other embodiments, the surfaceactive agent is present at a concentration of about 1% by weight up toabout 8% by weight of the total weight of the composition. In otherembodiments, the surface active agent is present at a concentration ofabout 1% by weight up to about 6% by weight of the total weight of thecomposition. In other embodiments, the surface active agent is presentat a concentration of about 1% by weight up to about 4% by weight of thetotal weight of the composition. In other embodiments, the surfaceactive agent is present at a concentration of about 20% by weight of thetotal weight of the composition. In other embodiments, the surfaceactive agent is present at a concentration of about 15% by weight of thetotal weight of the composition. In other embodiments, the surfaceactive agent is present at a concentration of about 13% by weight of thetotal weight of the composition. In other embodiments, the surfaceactive agent is present at a concentration of about 11% by weight of thetotal weight of the composition. In other embodiments, the surfaceactive agent is present at a concentration of about 8% by weight of thetotal weight of the composition. In other embodiments, the surfaceactive agent is present at a concentration of about 6% by weight of thetotal weight of the composition. In other embodiments, the surfaceactive agent is present at a concentration of about 4% by weight of thetotal weight of the composition. In other embodiments, the surfaceactive agent is present at a concentration of about 2% by weight of thetotal weight of the composition. In other embodiments, the surfaceactive agent is present at a concentration of about 1% by weight of thetotal weight of the composition.

The stable emulsions provided herein can contain one or more deliveryvehicles selected from among micelles, liposomes and cubosomes andmixtures thereof, that encapsulate the active agent. The deliveryvehicles encapsulating the active agent are then absorbed in theepithelium where the active agent is delivered.

d. Agents for Delivery

The compositions provided herein can contain one or more agents fordelivery to a subject. Generally the agents are those that confer abiological effect. Any agent that can be formulated as described hereincan be administered in the compositions provided herein. Where the agentis a therapeutic, the compositions contain a therapeutically effectiveamount of an agent to be delivered. The particular amount of activeagent in a dosage will vary widely according to the nature of the activeagent, the nature of the condition being treated, the age and size ofthe subject, and other parameters.

Generally, the amount of active agent in the composition will vary fromless than about 0.01% by weight to about 20% by weight of thecomposition or more and typically are formulated for single dosageadministration. A single dosage can vary from about 0.01 μg to 10 mg ofan agent per kilogram of body weight of the host, with dosages fromabout 0.1 μg to 1 mg/kg being commonly employed. These concentrations,however, are general guidelines only and particular amounts and dosagesmay be selected based on the active agent being administered, thecondition being treated, and the treatment regimen being employed. Theconcentration can be an amount of a drug or an active agent that issufficient to provide the desired local or systemic effect andperformance at a reasonable benefit/risk ratio to a subject attendingany medical treatment.

Agents for delivery are selected from inorganic and organic drugsincluding, but not limited to drugs that act on the peripheral nerves,adrenergic receptors, cholinergic receptors, nervous system, skeletalmuscles, cardiovascular system, smooth muscles, blood circulatorysystem, synaptic sites, neuro-effector junctional sites, endocrinesystem, hormone systems, immunological system, reproductive system,skeletal system, autocoid systems, alimentary and excretory systems,histamine systems, and the like. The active agents that can be deliveredusing the compositions provided herein include, but are not limited to,anticonvulsants, analgesics, antiparkinsons, anti-inflammatories,calcium antagonists, anesthetics, antimicrobials, antimalarials,antiparasitics, antihypertensives, antihistamines, antipyretics,alpha-adrenergic agonists, alpha-blockers, biocides, bactericides,bronchial dilators, beta-adrenergic blocking drugs, contraceptives,cardiovascular drugs, calcium channel inhibitors, depressants,diagnostics, diuretics, electrolytes, enzymes, hypnotics, hormones,hypoglycemics, hyperglycemics, muscle contractants, muscle relaxants,neoplastics, glycoproteins, nucleoproteins, lipoproteins, ophthalmics,psychic energizers, sedatives, steroids, sympathomimetics,parasympathomimetics, tranquilizers, urinary tract drugs, vaccines,vaginal drugs, vitamins, minerals, nonsteroidal anti-inflammatory drugs,angiotensin converting enzymes, polynucleotides, polypeptides,polysaccharides, and nutritional supplements including herbalsupplements.

The level of agent to be delivered is from about 0.01% up to about 50%,from about 0.1% up to about 40%, from about 0.1% up to about 30%, fromabout 0.1% up to about 20%, from about 0.1% up to about 10%, from about0.1% up to about 9%, from about 0.1% up to about 8%, from about 0.1% upto about 7%, from about 0.1% up to about 6%, from about 0.1% up to about5%, from about 0.1% up to about 4%, from about 0.1% up to about 3%, fromabout 0.1% up to about 2%, or from about 0.1% up to about 1% by weightof the composition. The agent to be delivered can be water soluble,slightly water soluble, or oil soluble. In certain embodiments, theagent to be delivered is selected from anticonvulsants, analgesics,antiparkinsons, anti-inflammatories, calcium antagonists, anesthetics,antimicrobials, antimalarials, antiparasitics, antihypertensives,antihistamines, antipyretics, alpha-adrenergic agonists, alpha-blockers,biocides, bactericides, bronchial dilators, beta-adrenergic blockingdrugs, contraceptives, cardiovascular drugs, calcium channel inhibitors,depressants, diagnostics, diuretics, electrolytes, enzymes, hypnotics,hormones, hypoglycemics, hyperglycemics, muscle contractants, musclerelaxants, neoplastics, glycoproteins, nucleoproteins, lipoproteins, nondenatured whey protein, ophthalmics, psychic energizers, sedatives,steroids, sympathomimetics, parasympathomimetics, tranquilizers, urinarytract drugs, vaccines, vaginal drugs, vitamins, minerals, nonsteroidalanti-inflammatory drugs, angiotensin converting enzymes,polynucleotides, polypeptides, polysaccharides, and nutritionalsupplements including herbal supplements.

In certain embodiments, the active agent is selected as follows:

α-Adrenergic agonists such as Adrafinil, Adrenolone, Amidephrine,Apraclonidine, Budralazine, Clonidine, Cyclopentamine, Detomidine,Dimetofrine, Dipivefrin, Ephedrine, Epinephrine, Fenoxazoline,Guanabenz, Guanfacine, Hydroxyamphetamine, Ibopamine, Indanazoline,Isometheptene, Mephentermine, Metaraminol, Methoxamine Hydrochloride,Methylhexaneamine, Metizolene, Midodrine, Naphazoline, Norepinephrine,Norfenefrine, Octodrine, Octopamine, Oxymetazoline, PhenylephrineHydrochloride, Phenylpropanolamine Hydrochloride,Phenylpropylmethylamine, Pholedrine, Propylhexedrine, Pseudoephedrine,Rilmenidine, Synephrine, Tetrahydrozoline, Tiamenidine, Tramazoline,Tuaminoheptane, Tymazoline, Tyramine and Xylometazoline;

β-Adrenergic agonists such as Albuterol, Bambuterol, Bitolterol,Carbuterol, Clenbuterol, Clorprenaline, Denopamine, Dioxethedrine,Dopexamine, Ephedrine, Epinephrine, Etafedrine, Ethylnorepinephrine,Fenoterol, Formoterol, Hexoprenaline, Ibopamine, Isoetharine,Isoproterenal, Mabuterol, Metaproterenol, Methoxyphenamine, Oxyfedrine,Pirbuterol, Prenalterol, Procaterol, Protokylol, Reproterol, Rimiterol,Ritodrine, Soterenol, Terbuterol and Xamoterol;

α-Adrenergic blockers such as Amosulalol, Arotinolol, Dapiprazole,Doxazosin, Ergoloid Mesylates, Fenspiride, Indoramin, Labetalol,Nicergoline, Prazosin, Terazosin, Tolazoline, Trimazosin and Yohimbine;

β-Adrenergic blockers such as Acebutolol, Alprenolol, Amosulalol,Arotinolol,

Atenolol, Befunolol, Betaxolol, Bevantolol, Bisoprolol, Bopindolol,Bucumolol, Befetolol, Bufuralol, Bunitrolol, Bupranolol, ButidrineHydrochloride, Butofilolol, Carazolol, Carteolol, Carvedilol,Celiprolol, Cetamolol, Cloranolol, Dilevalol, Epanolol, Esmolol,Indenolol, Labetalol, Levobunolol, Mepindolol, Metipranalol, Metoprolol,Moprolol, Nadoxolol, Nifenalol, Nipradilol, Oxprenolol, Penbutolol,Pindolol, Practolol, Pronethalol, Propranolol, Sotalol, Sulfinalol,Talinolol, Tertatolol, Timolol, Toliprolol and Xibenolol;

Alcohol deterrents such as Calcium Cyanamide Citrated, Disulfuram,Nadide and Nitrefazole;

Aldose reductase inhibitors such as Epalrestat, Ponalrestat, Sorbiniland Tolrestat;

Anabolics such as Androisoxazole, Androstenediol, Bolandiol,Bolasterone, Clostebol, Ethylestrenol; Formyldienolone,4-Hydroxy-19-nortestosterone, Methandriol, Methenolone,Methyltrienolone, Nandrolone, Nandrolone Decanoate, Nandrolonep-Hexyloxyphenylpropionate, Nandrolone Phenpropionate, Norbolethone,Oxymesterone, Pizotyline, Quinbolone, Stenbolone and Trenbolone;

Analgesics (dental) such as Chlorobutanol, Clove and Eugenol;

Analgesics (narcotic) such as Alfentanil, Allylprodine, Alphaprodine,Anileridine, Benzylmorphine, Bezitramide, Buprenorphine, Butorphanol,Clonitazene, Codeine, Codeine Methyl Bromide, Codeine Phosphate, CodeineSulfate, Desomorphine, Dextromoramide, Dezocine, Diampromide,Dihydrocodeine, Dihydrocodeinone Enol Acetate, Dihydromorphine,Dimenoxadol, Dimepheptanol, Dimethylthiambutene, Dioxaphetyl Butyrate,Dipipanone, Eptazocine, Ethoheptazine, Ethylmethlythiambutene,Ethylmorphine, Etonitazene, Fentanyl, Hydrocodone, HydrocodoneBitartrate, Hydromorphone, Hydroxypethidine, Isomethadone, Ketobemidone,Levorphanol, Lofentanil, Meperidine, Meptazinol, Metazocine, MethadoneHydrochloride, Metopon, Morphine, Morphine Derivatives, Myrophine,Nalbuphine, Narceine, Nicomorphine, Norlevorphanol, Normethadone,Normorphine, Norpipanone, Opium, Oxycodone, Oxymorphone, Papavereturn,Pentazocine, Phenadoxone, Phenazocine, Pheoperidine, Piminodine,Piritramide, Proheptazine, Promedol, Properidine, Propiram,Propoxyphene, Sufentanil and Tilidine;

Analgesics (non-narcotic) such as Acetaminophen, Acetaminosalol,Acetanilide, Acetylsalicylsalicylic Acid, Alclofenac, Alminoprofen,Aloxiprin, Aluminum Bis(acetylsalicylate), Aminochlorthenoxazin,2-Amino-4-picoline, Aminopropylon, Aminopyrine, Ammonium Salicylate,Antipyrine, Antipyrine Salicylate, Antrafenine, Apazone, Aspirin,Benorylate, Benoxaprofen, Benzpiperylon, Benzydamine,p-Bromoacetanilide, 5-Bromosalicylic Acid Acetate, Bucetin, Bufexamac,Bumadizon, Butacetin, Calcium Acetylsalicylate, Carbamazepine,Carbetidine, Carbiphene, Carsalam, Chloralantipyrine,Chlorthenoxazin(e), Choline Salicylate, Cinchophen, Ciramadol,Clometacin, Cropropamide, Crotethamide, Dexoxadrol, Difenamizole,Diflunisal, Dihydroxyaluminum Acetylsalicylate, Dipyrocetyl, Dipyrone,Emorfazone, Enfenamic Acid, Epirizole, Etersalate, Ethenzamide,Ethoxazene, Etodolac, Felbinac, Fenoprofen, Floctafenine, FlufenamicAcid, Fluoresone, Flupirtine, Fluproquazone, Flurbiprofen, Fosfosal,Gentisic Acid, Glafenine, Ibufenac, Imidazole Salicylate, Indomethacin,Indoprofen, Isofezolac, Isoladol, Isonixin, Ketoprofen, Ketorolac,p-Lactophenetide, Lefetamine, Loxoprofen, Lysine Acetylsalicylate,Magnesium Acetylsalicylate, Methotrimeprazine, Metofoline, Miroprofen,Morazone, Morpholine Salicylate, Naproxen, Nefopam, Nifenazone, 5′Nitro-2′ propoxyacetanilide, Parsalmide, Perisoxal, Phenacetin,Phenazopyridine Hydrochloride, Phenocoll, Phenopyrazone, PhenylAcetylsalicylate, Phenyl Salicylate, Phenyramidol, Pipebuzone,Piperylone, Prodilidine, Propacetamol, Propyphenazone, Proxazole,Quinine Salicylate, Ramifenazone, Rimazolium Metilsulfate, Salacetamide,Salicin, Salicylamide, Salicylamide O-Acetic Acid, Salicylsulfuric Acid,Salsalte, Salverine, Simetride, Sodium Salicylate, Sulfamipyrine,Suprofen, Talniflumate, Tenoxicam, Terofenamate, Tetradrine, Tinoridine,Tolfenamic Acid, Tolpronine, Tramadol, Viminol, Xenbucin and Zomepirac;

Androgens such as Androsterone, Boldenone, Dehydroepiandrosterone,Fluoxymesterone, Mestanolone, Mesterolone, Methandrostenolone,17-Methyltestosterone, 17α-Methyltestosterone 3-Cyclopentyl Enol Ether,Norethandrolone, Normethandrone, Oxandrolone, Oxymesterone,Oxymetholone, Prasterone, Stanlolone, Stanozolol, Testosterone,Testosterone 17-Chloral Hemiacetal, Testosterone 17β-Cypionate,Testosterone Enanthate, Testosterone Nicotinate, TestosteronePheynylacetate, Testosterone Propionate and Tiomesterone;

Anesthetics such as Acetamidoeugenol, Alfadolone Acetate, Alfaxalone,Amucaine, Amolanone, Amylocalne Hydrochloride, Benoxinate, Benzocaine,Betoxycaine, Biphenamine, Bupivacaine, Butacaine, Butaben,Butanilicaine, Burethamine, Buthalital Sodium, Butoxycaine, Carticaine,2-Chloroprocaine Hydrochloride, Cocaethylene, Cocaine, Cyclomethycaine,Dibucaine Hydrochloride, Dimethisoquin, Dimethocaine, DiperadonHydrochloride, Dyclonine, Ecgonidine, Ecgonine, Ethyl Aminobenzoate,Ethyl Chloride, Etidocaine, Etoxadrol, β-Eucaine, Euprocin, Fenalcomine,Fomocaine, Hexobarbital, Hexylcaine Hydrochloride, Hydroxydione Sodium,Hydroxyprocaine, Hydroxytetracaine, Isobutyl p-Aminobenzoate, Kentamine,Leucinocaine Mesylate, Levoxadrol, Lidocaine, Mepivacaine, MeprylcaineHydrochloride, Metabutoxycaine Hydrochloride, Methohexital Sodium,Methyl Chloride, Midazolam, Myrtecaine, Naepaine, Octacaine, Orthocaine,Oxethazaine, Parethoxycaine, Phenacaine Hydrochloride, Phencyclidine,Phenol, Piperocaine, Piridocaine, Polidocanol, Pramoxine, Prilocalne,Procaine, Propanidid, Propanocaine, Proparacaine, Propipocaine,Propofol, Propoxycaine Hydrochloride, Pseudococaine, Pyrrocaine, QuinineUrea Hydrochloride, Risocaine, Salicyl Alcohol, TetracaineHydrochloride, Thialbarbital, Thimylal, Thiobutabarbital, ThiopentalSodium, Tolycaine, Trimecaine and Zolamine;

Anorexics such as A minorex, Amphecloral, Amphetamine, Benzaphetamine,Chlorphentermine, Clobenzorex, Cloforex, Clortermine, Cyclexedrine,Destroamphetamine Sulfate, Diethylpropion, Diphemethoxidine,N-Ethylamphetamine, Fenbutrazate, Fenfluramine, Fenproporex,Furfurylmethylamphetamine, Levophacetoperate, Mazindol, Mefenorex,Metamfeproamone, Methamphetamine, Norpseudoephedrine, Phendimetrazine,Phendimetrazine Tartrate, Phenmetrazine, Phenpentermine,Phenylpropanolamine Hydrochloride and Picilorex;

Anthelmintics (Cestodes) such as Arecoline, Aspidin, Aspidinol,Dichlorophen(e), Embelin, Kosin, Napthalene, Niclosamide, Pellertierine,Pellertierine Tannate and Quinacrine;

Anthelmintics (Nematodes) such as Alantolactone, Amoscanate, Ascaridole,Bephenium, Bitoscanate, Carbon Tetrachloride, Carvacrol, Cyclobendazole,Diethylcarbamazine, Diphenane, Dithiazanine Iodide, Dymanthine, GentianViolet, 4-Hexylresorcinol, Kainic Acid, Mebendazole, 2-Napthol, Oxantel,Papain, piperazine, piperazine Adipate, piperazine Citrate, piperazineEdetate Calcium, piperazine Tartrate, Pyrantel, Pyrvinium Pamoate,α-Santonin, Stilbazium Iodide, Tetrachloroethylene, Tetramisole,thiabendazole, Thymol, Thymyl N-Isoamylcarbamate, Triclofenol piperazineand Urea Stibamine;

Anthelmintics (Onchocerca) such as Ivermectin and Suramin Sodium;

Anthelmintics (Schistosoma) such as Amoscanate, Amphotalide, AntimonyPotassium Tartrate, Antimony Sodium Gluconate, Antimony Sodium Tartrate,Antimony Sodium Thioglycollate, Antimony Thioglycollamide, Becanthone,Hycanthone, Lucanthone Hydrochloride, Niridazole, Oxamniquine,Praziquantel, Stibocaptate, Stibophen and Urea Stibamine;

Anthelmintics (Trematodes) such as Anthiolimine and Tetrachloroethylene;

Antiacne drugs such as Adapelene, Algestone Acetophenide, Azelaic Acid,Benzoyl Peroxide, Cyoctol, Cyproterone, Motretinide, Resorcinol,Retinoic Acid, Tetroquinone and Tretinonine;

Antiallergics such as Amlexanox, Astemizole, Azelastine, Cromolyn,Fenpiprane, Histamine, Ibudilast, Nedocromil, Oxatomide, Pentigetide,Poison Ivy Extract, Poison Oak Extract, Poison Sumac Extract,Repirinast, Tranilast, Traxanox and Urushiol;

Antiamebics such as Arsthinol, Bialamicol, Carbarsone, Cephaeline,Chlorbetamide, Chloroquine, Chlorphenoxamide, Chlortetracycline,Dehydroemetine, Dibromopropamidine, Diloxanide, Dephetarsone, Emetine,Fumagillin, Glaucarubin, Glycobiarsol,8-Hydroxy-7-iodo-5-quinolinesulfonic Acid, Iodochlorhydroxyquin,Iodoquinol, Paromomycin, Phanquinone, Phearsone Sulfoxylate,Polybenzarsol, Propamidine, Quinfamide, Secnidazole, Sulfarside,Teclozan, Tetracycline, Thiocarbamizine, Thiocarbarsone and Timidazole;

Antiandrogens such as Bifluranol, Cyoctol, Cyproterone, DelmadinoneAcetate, Flutimide, Nilutamide and Oxendolone;

Antianginals such as Acebutolol, Alprenolol, Amiodarone, Amlodipine,Arotinolol, Atenolol, Bepridil, Bevantolol, Bucumolol, Bufetolol,Bufuralol, Bunitrolol, Bupranolol, Carazolol, Carteolol, Carvedilol,Celiprolol, Cinepazet Maleate, Diltiazem, Epanolol, Felodipine,Gallopamil, Imolamine, Indenolol, Isosorbide Dinitrate, Isradipine,Limaprost, Mepindolol, Metoprolol, Molsidomine, Nadolol, Nicardipine,Nifedipine, Nifenalol, Nilvadipine, Nipradilol, Nisoldipine,Nitroglycerin, Oxprenolol, Oxyfedrine, Ozagrel, Penbutolol,Pentaerythritol Tetranitrate, Pindolol, Pronethalol, Propranolol,Sotalol, Terodiline, Timolol, Toliprolol and Verapamil;

Antiarrhythmics such as Acebutolol, Acecaine, Adenosine, Ajmaline,Alprenolol, Amiodarone, Amoproxan, Aprindine, Arotinolol, Atenolol,Bevantolol, Bretylium Tosylate, Bucumolol, Bufetolol, Bunaftine,Bunitrolol, Bupranolol, Butidrine Hydrochloride, Butobendine, CapobenicAcid, Carazolol, Carteolol, Cifenline, Cloranolol, Disopyramide,Encamide, Esmolol, Flecamide, Gallopamil, Hydroquinidine, Indecamide,Indenolol, Ipratropium Bromide, Lidocaine, Lorajmine, Lorcamide,Meobentine, Metipranolol, Mexiletine, Moricizine, Nadoxolol, Nifenalol,Oxprenolol, Penbutolol, Pindolol, Pirmenol, Practolol, Prajmaline,Procainamide Hydrochloride, Pronethalol, Propafenone, Propranolol,Pyrinoline, Quinidine Sulfate, Quinidine, Sotalol, Talinolol, Timolol,Tocamide, Verapamil, Viquidil and Xibenolol;

Antiarteriosclerotics such as Pyridinol Carbamate;

Antiarthritic/Antirheumatics such as Allocupreide Sodium, Auranofin,Aurothioglucose, Aurothioglycanide, Azathioprine, Calcium3-Aurothio-2-propanol-1-sulfonate, Celecoxib, Chloroquine, Clobuzarit,Cuproxoline, Diacerein, Glucosamine, Gold Sodium Thiomalate, Gold SodiumThiosulfate, Hydroxychloroquine, Kebuzone, Lobenzarit, Melittin,Methotrexate, Myloral and Penicillamine;

Antibacterial (antibiotic) drugs including: Aminoglycosides such asAmikacin, Apramycin, Arbekacin, Bambermycins, Butirosin, Dibekacin,Dihydrostreptomycin, Fortimicin(s), Gentamicin, Isepamicin, Kanamycin,Micronomicin, Neomycin, Neomycin Undecylenate, Netilmicin, Paromomycin,Ribostamycin, Sisomicin, Spectinomycin, Streptomycin, Streptonicozid andTobramycin;

Amphenicols such as Azidamfenicol, Chloramphenicol, ChloramphenicolPalmitate, Chloramphenicol Pantothenate, Florfenicol and Thiamphenicol;

Ansamycins such as Rifamide, Rifampin, Rifamycin and Rifaximin;

β-Lactams, including: Carbapenems such as Imipenem;

Cephalosporins such as Cefactor, Cefadroxil, Cefamandole, Cefatrizine,Cefazedone, Cefazolin, Cefixime, Cefinenoxime, Cefodizime, Cefonicid,Cefoperazone, Ceforanide, Cefotaxime, Cefotiam, Cefpimizole,Cefpiramide, Cefpodoxime Proxetil, Cefroxadine, Cefsulodin, Ceftazidime,Cefteram, Ceftezole, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefuroxime,Cefuzonam, Cephacetrile Sodium, Cephalexin, Cephaloglycin,Cephaloridine, Cephalosporin, Cephalothin, Cephapirin Sodium, Cephradineand Pivcefalexin;

Cephamycins such as Cefbuperazone, Cefinetazole, Cefminox, Cefotan andCefoxitin;

Monobactams such as Aztreonam, Carumonam and Tigemonam;

Oxacephems such as Flomoxef and Moxalactam;

Penicillins such as Amdinocillin, Amdinocillin Pivoxil, Amoxicillin,Ampicillin, Apalcillin, Aspoxicillin, Azidocillin, Azlocillin,Bacampicillin, Benzylpenicillinic Acid, Benzylpenicillin Sodium,Carbenicillin, Carfecillin Sodium, Carindacillin, Clometocillin,Cloxacillin, Cyclacillin, Dicloxacillin, Diphenicillin Sodium,Epicillin, Fenbenicillin, Floxacillin, Hetacillin, Lenampicillin,Metampicillin, Methicillin Sodium, Mezlocillin, Nafcillin Sodium,Oxacillin, Penamecillin, Penethamate Hydriodide, Penicillin GBenethamine, Penicillin G Benzathine, Penicillin G Benzhydrylamine,Penicillin G Calcium, Penicillin G Hydrabamine, Penicillin G Potassium,Penicillin G Procaine, Penicillin N, Penicillin O, Penicillin V,Penicillin V Benzathine, Penicillin V Hydrabamine, Penimepicycline,Phenethicillin Potassium, Piperacillin, Pivampicillin, Propicillin,Quinacillin, Sulbenicillin, Talampicillin, Temocillin and Ticarcillin;

Lincosamides such as Clindamycin and Lincomycin;

Macrolides such as Azithromycin, Carbomycin, Clarithromycin,Erythromycin, Erythromycin Acistrate, Erythromycin Estolate,Erythromycin Glucoheptonate, Erythromycin Lactobionate, ErythromycinPropionate, Erythromycin Stearate, Josamycin, Leucomycins, Midecamycins,Miokamycin, Oleandomycin, Primycin, Rokitamycin, Rosaramicin,Roxithromycin, Spiramycin and Troleandomycin;

Polypeptides such as Amphomycin, Bacitracin, Capreomycin, Colistin,Enduracidin, Enviomycin, Fusafungine, Gramicidin(s), Gramicidin S,Mikamycin, Polymyxin, Polymyxin B-Methanesulfonic Acid, Pristinamycin,Ristocetin, Teicoplanin, Thiostrepton, Tuberactinomycin, Tyrocidine,Tyrothricin, Vancomycin, Viomycin, Viomycin Pantothenate, Virginiamycinand Zinc Bacitracin;

Tetracyclines such as Apicycline, Chlortetracycline, Clomocycline,Demeclocycline, Doxycycline, Guamecycline, Lymecycline, Meclocycline,Methacycline, Minocycline, Oxytetracycline, Penimepicycline,Pipacycline, Rolitetracycline, Sancycline, Senociclin and Tetracycline;and

other antibiotics such as Cycloserine, Mupirocin and Tuberin;

Antibacterial drugs (synthetic), including: 2,4-Diaminopyrimidines suchas Brodimoprim, Tetroxoprim and Trimethoprim;

Nitrofurans such as Furaltadone, Furazolium Chloride, Nifuradene,Nifuratel, Nifurfoline, Nifurpirinol, Nifurprazine, Nifurtoinol andNitrofurantoin;

Quinolones and Analogs such as Amifloxacin, Cinoxacin, Ciprofloxacin,Difloxacin, Enoxacin, Fleroxacin, Flumequine, Lomefloxacin, Miloxacin,Nalidixic Acid, Norfloxacin, Ofloxacin, Oxolinic Acid, Pefloxacin,Pipemidic Acid, Piromidic Acid, Rosoxacin, Temafloxacin andTosufloxacin;

Sulfonamides such as Acetyl Sulfamethoxypyrazine, Acetyl Sulfisoxazole,Azosulfamide, Benzylsulfamide, Chloramine-B, Chloramine-T, DichloramineT, Formosulfathiazole, N₂ Formylsulfisomidine,N²-β-D-Glucosylsulfanilamide, Mafenide,4′-(Methylsulfamoyl)sulfanilanilide, p-Nitrosulfathiazole,Noprylsulfamide, Phthalylsulfacetamide, Phthalylsulfathiazole,Salazosulfadimidine, Succinylsulfathiazole, Sulfabenzamide,Sulfacetamide, Sulfachlorpyridazine, Sulfachrysoidine, Sulfacytine,Sulfadiazine, Sulfadicramide, Sulfadimethoxine, Sulfadoxine,Sulfaethidole, Sulfaguanidine, Sulfaguanole, Sulfalene, Sulfaloxic Acid,Sulfamerazine, Sulfameter, Sulfamethazine, Sulfamethizole,Sulfamethomidine, Sulfamethoxazole, Sulfamethoxypyridazine,Sulfametrole, Sulfamidochrysoidine, Sulfamoxole, Sulfanilamide,Sulfanilamidomethanesulfonic Acid Triethanolamine Salt,4-Sulfanilamidosalicylic Acid, N-Sulfanilylsulfanilamide,Sulfanilylurea, N-Sulfanilyl-3,4-xylamide, Sulfanitran, Sulfaperine,Sulfaphenazole, Sulfaproxyline, Sulfapyrazine, Sulfapyridine,Sulfasomizole, Sulfasymazine, Sulfathiazole, Sulfathiourea,Sulfatolamide, Sulfisomidine and Sulfisoxazole;

Sulfones such as Acedapsone, Acediasulfone, Acetosulfone Sodium,Dapsone, Diathymosulfone, Glucosulfone Sodium, Solasulfone,Succisulfone, Sulfanilic Acid, p-Sulfanilylbenzylamine,p,p′-Sulfonyldianiline-N,N′ digalactoside, Sulfoxone Sodium andThiazolsulfone; and

others such as Clofoctol, Hexedine, Methenamine, MethenamineAnhydromethylene-citrate, Methenamine Hippurate, Methenamine Mandelate,Methenamine Sulfosalicylate, Nitroxoline and Xibornol;

Anticholinergics such as Adiphenine Hydrochloride, Alverine,Ambutonomium Bromide, Aminopentamide, Amixetrine, AmprotropinePhosphate, Anisotropine Methylbromide, Apoatropine, Atropine, AtropineN-Oxide, Benactyzine, Benapryzine, Benzetimide, Benzilonium Bromide,Benztropine Mesylate, Bevonium Methyl Sulfate, Biperiden, ButropiumBromide, N-Butylscopolammonium Bromide, Buzepide, Camylofine, CaramiphenHydrochloride, Chlorbenzoxamine, Chlorphenoxamine, Cimetropium Bromide,Clidinium Bromide, Cyclodrine, Cyclonium Iodide, CycrimineHydrochloride, Deptropine, Dexetimide, Dibutoline Sulfate, DicyclomineHydrochloride, Diethazine, Difemerine, Dihexyverine, DiphemanilMethylsulfate, N-(1,2-Diphenylethyl)nicotinamide, Dipiproverine,Diponium Bromide, Emepronium Bromide, Endobenzyline Bromide,Ethopropazine, Ethybenztropine, Ethylbenzhydramine, Etomidoline,Eucatropine, Fenpiverinium Bromide, Fentonium Bromide, FlutropiumBromide, Glycopyrrolate, Heteronium Bromide, Hexocyclium Methyl Sulfate,Homatropine, Hyoscyamine, Ipratropium Bromide, Isopropamide, Levomepate,Mecloxamine, Mepenzolate Bromide, Metcaraphen, Methantheline Bromide,Methixene, Methscopolamine Bromide, Octamylamine, Oxybutynin Chloride,Oxyphencyclimine, Oxyphenonium Bromide, Pentapiperide, PenthienateBromide, Phencarbamide, Phenglutarimide, Pipenzolate Bromide,Piperidolate, Piperilate, Poldine Methysulfate, Pridinol, PrifiniumBromide, Procyclidine, Propantheline Bromide, Propenzolate,Propyromazine, Scopolamine, Scopolamine N-Oxide, Stilonium Iodide,Stramonium, Sultroponium, Thihexinol, Thiphenamil, Tiemonium Iodide,Timepidium Bromide, Tiquizium Bromide, Tridihexethyl Iodide,Trihexyphenidyl Hydrochloride, Tropacine, Tropenzile, Tropicamide,Trospium Chloride, Valethamate Bromide and Xenytropium Bromide;

Anticonvulsants such as Acetylpheneturide, Albutoin, Aloxidone,Aminoglutethimide, 4-Amino-3-hydroxybutyric Acid, Atrolactamide,Beclamide, Buramate, Calcium Bromide, Carbamazepine, Cinromide,Clomethiazole, Clonazepam, Decimemide, Diethadione, Dimethadione,Doxenitoin, Eterobarb, Ethadione, Ethosuximide, Ethotoin, Fluoresone,Garbapentin, 5-Hydroxytryptophan, Lamotrigine, Lamictal, MagnesiumBromide, Magnesium Sulfate, Mephenyloin, Mephobarbital, Metharbital,Methetoin, Methsuximide, 5-Methyl-5-(3-phenanthryl)hydantoin,3-Methyl-5-phenylhydantoin, Narcobarbital, Nimetazepam, Nitrazepam,Paramethadione, Phenacemide, Phenetharbital, Pheneturide, Phenobarbital,Phenobarbital Sodium, Phensuximide, Phenylmethylbarbituric Acid,Phenyloin, Phethenylate Sodium, Potassium Bromide, Pregabalin,Primidone, Progabide, Sodium Bromide, Sodium Valproate, Solanum,Strontium Bromide, Suclofenide, Sulthiame, Tetrantoin, Tiagabine,Trimethadione, Valproic Acid, Valpromide, Vigabatrin and Zonisamide;

Antidepressants, including: Bicyclics such as Binedaline, Caroxazone,Citalopram, Dimethazan, Indalpine, Fencamine, Fluvoxamine Maleate,Indeloxazine Hydrochloride, Nefopam, Nomifensine, Oxitriptan,Oxypertine, Paroxetine, Sertraline, Thiazesim, Trazodone, Venlafaxineand Zometapine;

Hydrazides/Hydrazines such as Benmoxine, Iproclozide, Iproniazid,Isocarboxazid, Nialamide, Octamoxin and Phenelzine;

Pyrrolidones such as Cotinine, Rolicyprine and Rolipram;

Tetracyclics such as Maprotiline, Metralindole, Mianserin andOxaprotiline;

Tricyclics such as Adinazolam, Amitriptyline, Amitriptylinoxide,Amoxapine, Butriptyline, Clomipramine, Demexiptiline, Desipramine,Dibenzepin, Dimetracrine, Dothiepin, Doxepin, Fluacizine, Imipramine,Imipramine N-Oxide, Iprindole, Lofepramine, Melitracen, Metapramine,Nortriptyline, Noxiptilin, Opipramol, Pizotyline, Propizepine,Protriptyline, Quinupramine, Tianeptine and Trimipramine; and

others such as Adrafinil, Benactyzine, Bupropion, Butacetin, Deanol,Deanol Aceglumate, Deanol Acetamidobenzoate, Dioxadrol, Etoperidone,Febarbamate, Femoxetine, Fenpentadiol, Fluoxetine, Fluvoxamine,Hematoporphyrin, Hypercinin, Levophacetoperane, Medifoxamine, Minaprine,Moclobemide, Oxaflozane, Piberaline, Prolintane, Pyrisuccideanol,Rubidium Chloride, Sulpiride, Sultopride, Teniloxazine, Thozalinone,Tofenacin, Toloxatone, Tranylcypromine, L-Tryptophan, Viloxazine andZimeldine;

Antidiabetics, including: Biguanides such as Buformin, Metformin andPhenformin;

Hormones such as Glucagon, Insulin, Insulin Injection, Insulin ZincSuspension, Isophane Insulin Suspension, Protamine Zinc InsulinSuspension and Zinc Insulin Crystals;

Sulfonylurea derivatives such as Acetohexamide, 1-Butyl-3-metanilylurea,Carbutamide, Chlorpropamide, Glibornuride, Gliclazide, Glipizide,Gliquidone, Glisoxepid, Glyburide, Glybuthiazol(e), Glybuzole,Glyhexamide, Glymidine, Glypinamide, Phenbutamide, Tolazamide,Tolbutamide and Tolcyclamide; and

others such as Acarbose, Calcium Mesoxalate and Miglitol;

Antidiarrheal drugs such as Acetyltannic Acid, Albumin Tannate,Alkofanone, Aluminum Salicylates—Basic, Catechin, Difenoxin,Diphenoxylate, Lidamidine, Loperamide, Mebiquine, Trillium and Uzarin;

Antidiuretics such as Desmopressin, Felypressin, Lypressin, Ornipressin,Oxycinchophen, Pituitary—Posterior, Terlipressin and Vasopressin;

Antiestrogens such as Delmadinone Acetate, Ethamoxytriphetol, Tamoxifenand Toremifene;

Antifungal drugs (antibiotics), including: Polyenes such asAmphotericin-B, Candicidin, Dermostatin, Filipin, Fungichromin,Hachimycin, Hamycin, Lucensomycin, Mepartricin, Natamycin, Nystatin,Pecilocin and Perimycin; and others such as Azaserine, Griseofulvin,Oligomycins, Neomycin Undecylenate, PyrroInitrin, Siccanin, Tubercidinand Viridin;

Antifungal drugs (synthetic), including: Allylamines such as Naftifineand Terbinafine;

Imidazoles such as Bifonazole, Butoconazole, Chlordantoin,Chlormidazole, Cloconazole, Clotrimazole, Econazole, Enilconazole,Fenticonazole, Isoconazole, Ketoconazole, Miconazole, Omoconazole,Oxiconazole, Nitrate, Sulconazole and Tioconazole;

Triazoles such as Fluconazole, Itraconazole and Terconazole; and otherssuch as Acrisorcin, Amorolfine, Biphenamine, Bromosalicylchloranilide,Buclosamide, Calcium Propionate, Chlorphenesin, Ciclopirox, Cloxyquin,Coparaffinate, Diamthazole, Dihydrochloride, Exalamide, Flucytosine,Halethazole, Hexetidine, Loflucarban, Nifuratel, Potassium Iodide,Propionic Acid, Pyrithione, Salicylanilide, Sodium Propionate,Sulbentine, Tenonitrozole, Tolciclate, Tolindate, Tolnaftate, Tricetin,Ujothion, Undecylenic Acid and Zinc Propionate;

Antiglaucoma drugs such as Acetazolamide, Befunolol, Betaxolol,Bupranolol, Carteolol, Dapiprazoke, Dichlorphenamide, Dipivefrin,Epinephrine, Levobunolol, Methazolamide, Metipranolol, Pilocarpine,Pindolol and Timolol;

Antigonadotropins such as Danazol, Gestrinone and Paroxypropione;

Antigout drugs such as Allopurinol, Carprofen, Colchicine, Probenecidand Sulfinpyrazone;

Antihistamines, including: Alkylamine derivatives such as Acrivastine,Bamipine, Brompheniramine, Chlorpheniramine, Dimethindene, Metron S,Pheniramine, Pyrrobutamine, Thenaldine, Tolpropamine and Triprolidine;

Aminoalkyl ethers such as Bietanautine, Bromodiphenhydramine,Carbinoxamine, Clemastine, Diphenylpyraline, Doxylamine, Embramine,Medrylamine, Mephenphydramine, p-Methyldiphenhydramine, Orphenadrine,Phenyltoloxamine, Piprinhydrinate and Setasine;

Ethylenediamine derivatives such as Alloclamide, p-Bromtripelennamine,Chloropyramine, Chlorothen, Histapyrrodine, Methafurylene,Methaphenilene, Methapyrilene, Phenbenzamine, Pyrilamine, Talastine,Thenyldiamine, Thonzylamine Hydrochloride, Tripelennamine and Zolamine;

Piperazines such as Cetirizine, Chlorcyclizine, Cinnarizine, Clocinizineand Hydroxyzine;

Tricyclics, including: Phenothiazines such as Ahistan, Etymemazine,Fenethazine, N-Hydroxyethylpromethazine Chloride, Isopromethazine,Mequitazine, Promethazine, Pyrathiazine and Thiazinamium Methyl Sulfate;and

others such as Azatadine, Clobenzepam, Cyproheptadine, Deptropine,Isothipendyl, Loratadine and Prothipendyl; and

other antihistamines such as Antazoline, Astemizole, Azelastine,Cetoxime, Clemizole, Clobenztropine, Diphenazoline, Diphenhydramine,Fluticasone Propionate, Mebhydroline, Phenindamine, Terfenadine andTritoqualine;

Antihyperlipoproteinemics, including: Aryloxyalkanoic acid derivativessuch as Beclorbrate, Bezafibrate, Binifibrate, Ciprofibrate,Clinofibrate, Clofibrate, Clofibric Acid, Etofibrate, Fenofibrate,Gemfibrozil, Nicofibrate, Pirifibrate, Ronifibrate, Simfibrate andTheofibrate;

Bile acid sequesterants such as Cholestyramine Resin, Colestipol andPolidexide;

HMG CoA reductase inhibitors such as Fluvastatin, Lovastatin,Pravastatin Sodium and Simvastatin;

Nicotinic acid derivatives Aluminum Nicotinate, Acipimox, Niceritrol,Nicoclonate, Nicomol and Oxiniacic Acid;

Thyroid hormones and analogs such as Etiroxate, Thyropropic Acid andThyroxine; and

others such as Acifran, Azacosterol, Benfluorex, β-Benzalbutyramide,Carnitine, Chondroitin Sulfate, Clomestone, Detaxtran, Dextran SulfateSodium, 5,8,11,14,17-Eicosapentaenoic Acid, Eritadenine, Furazabol,Meglutol, Melinamide, Mytatrienediol, Ornithine, γ-Oryzanol, Pantethine,Pentaerythritol Tetraacetate, α-Phenylbutyramide, Pirozadil, Probucol,α-Sitosterol, Sultosilic Acid, piperazine Salt, Tiadenol, Triparanol andXenbucin;

Antihypertensive drugs, including: Arylethanolamine derivatives such asAmosulalol, Bufuralol, Dilevalol, Labetalol, Pronethalol, Sotalol andSulfinalol;

Aryloxypropanolamine derivatives such as Acebutolol, Alprenolol,Arotinolol, Atenolol, Betaxolol, Bevantolol, Bisoprolol, Bopindolol,Bunitrolol, Bupranolol, Butofilolol, Carazolol, Cartezolol, Carvedilol,Celiprolol, Cetamolol, Epanolol, Indenolol, Mepindolol, Metipranolol,Metoprolol, Moprolol, Nadolol, Nipradilol, Oxprenolol, Penbutolol,Pindolol, Propranolol, Talinolol, Tetraolol, Timolol and Toliprolol;

Benzothiadiazine derivatives such as Althiazide, Bendroflumethiazide,Benzthiazide, Benzylhydrochlorothiazide, Buthiazide, Chlorothiazide,Chlorthalidone, Cyclopenthiazide, Cyclothiazide, Diazoxide, Epithiazide,Ethiazide, Fenquizone, Hydrochlorothiazide, Hydroflumethiazide,Methyclothiazide, Meticrane, Metolazone, Paraflutizide, Polythiazide,Tetrachlormethiazide and Trichlormethiazide;

N-Carboxyalkyl (peptide/lactam) derivatives such as Alacepril,Captopril, Cilazapril, Delapril, Enalapril, Enalaprilat, Fosinopril,Lisinopril, Moveltipril, Perindopril, Quinapril and Ramipril;

Dihydropyridine derivatives such as Amlodipine, Felodipine, Isradipine,Nicardipine, Nifedipine, Nilvadipine, Nisoldipine and Nitrendipine;

Guanidine derivatives such as Bethanidine, Debrisoquin, Guanabenz,Guanacline, Guanadrel, Guanazodine, Guanethidine, Guanfacine,Guanochlor, Guanoxabenz and Guanoxan;

Hydrazines and phthalazines such as Budralazine, Cadralazine,Dihydralazine, Endralazine, Hydracarbazine, Hydralazine, Pheniprazine,Pildralazine and Todralazine;

Imidazole derivatives such as Clonidine, Lofexidine, Phentolamine,Phentolamine Mesylate, Tiamenidine and Tolonidine;

Quaternary ammonium compounds Azamethonium Bromide, ChlorisondamineChloride, Hexamethonium, Pentaćynium Bis(methyl sulfate), PentamethoniumBromide, Pentolinium Tartrate, Phenactropinium Chloride andTrimethidinium Methosulfate;

Quinazoline derivatives such as Alfuzosin, Bunazosin, Doxazosin,Prasosin, Terazosin and Trimazosin;

Reserpine derivatives such as Bietaserpine, Deserpidine, Rescinnamine,Reserpine and Syrosingopine;

Sulfonamide derivatives such as Ambuside, Clopamide, Furosemide,Indapamide, Quinethazone, Tripamide and Xipamide; and

others such as Ajmaline, γ-Aminobutyric Acid, Bufeniode, Candesartan,Chlorthalidone, Cicletanine, Ciclosidomine, Cryptenamine Tannates,Eprosartan, Fenoldopam, Flosequinan, Indoramin, Irbesartan, Ketanserin,Losartan, Mebutamate, Mecamylamine, Methyldopa, Methyl 4-Pyridyl KetoneThiosemicarbazone, Metolazone, Minoxidil, Muzolimine, Pargyline,Pempidine, Pinacidil, Piperoxan, Primaperone, Protoveratrines,Raubasine, Rescimetol, Rilmenidine, Saralasin, Sodium Nitroprusside,Ticrynafen, Trimethaphan Camsylate, Tyrosinase, Urapidil and Valsartan;

Antihyperthyroids such as 2-Amino-4-methylthiazole, 2-Aminothiazole,Carbimazole, 3,5-Dibromo-L-tyrosine, 3,5-Diiodotyrosine, Hinderin,Iodine, Iothiouracil, Methimazole, Methylthiouracil, Propylthiouracil,Sodium Perchlorate, Thibenzazoline, Thiobarbital and 2-Thiouracil;

Antihypotensive drugs such as Amezinium Methyl Sulfate, AngiotensinAmide, Dimetofrine, Dopamine, Etifelmine, Etilefrine, Gepefrine,Metaraminol, Midodrine, Norepinephrine, Pholedrine and Synephrine;

Antihypothyroid drugs such as Levothyroxine Sodium, Liothyronine,Thyroid, Thyroidin, Thyroxine, Tiratricol and TSH;

Anti-Inflammatory (non-steroidal) drugs, including: Aminoarylcarboxylicacid derivatives such as Enfenamic Acid, Etofenamate, Flufenamic Acid,Isonixin, Meclofenamic Acid, Mefanamic Acid, Niflumic Acid,Talniflumate, Terofenamate and Tolfenamic Acid;

Arylacetic acid derivatives such as Acemetacin, Alclofenac, Amfenac,Bufexamac, Cinmetacin, Clopirac, Diclofenac Sodium, Etodolac, Felbinac,Fenclofenac, Fenclorac, Fenclozic Acid, Fentiazac, Glucametacin,Ibufenac, Indomethacin, Isofezolac, Isoxepac; Lonazolac, MetiazinicAcid, Oxametacine, Proglumetacin, Sulindac, Tiaramide, Tolmetin andZomepirac;

Arylbutyric acid derivatives such as Bumadizone, Butibufen, Fenbufen andXenbucin;

Arylcarboxylic acids such as Clidanac, Ketorolac and Tinoridine;

Arylpropionic acid derivatives such as Alminoprofen, Benoxaprofen,Bucloxic Acid, Carprofen, Fenoprofen, Flunoxaprofen, Flurbiprofen,Ibuprofen, Ibuproxam, Indoprofen, Ketoprofen, Loxoprofen, Miroprofen,Naproxen, Oxaprozin, Piketoprofen, Pirprofen, Pranoprofen, ProtizinicAcid, Suprofen and Tiaprofenic Acid;

Pyrazoles such as Difenamizole and Epirizole;

Pyrazolones such as Apazone, Benzpiperylon, Feprazone, Mofebutazone,Morazone, Oxyphenbutazone, Phenybutazone, Pipebuzone, Propyphenazone,Ramifenazone, Suxibuzone and Thiazolinobutazone;

Salicylic acid derivatives such as Acetaminosalol, Aspirin, Benorylate,Bromosaligenin, Calcium Acetylsalicylate, Diflunisal, Etersalate,Fendosal, Gentisic Acid, Glycol Salicylate, Imidazole Salicylate, LysineAcetylsalicylate, Mesalamine, Morpholine Salicylate, 1-NaphthylSalicylate, Olsalazine, Parsalmide, Phenyl Acetylsalicylate, PhenylSalicylate, Salacetamide, Salicylamine O-Acetic Acid, SalicylsulfuricAcid, Salsalate and Sulfasalazine;

Thiazinecarboxamides such as Droxicam, Isoxicam, Piroxicam andTenoxicam; and others such as ε-Acetamidocaproic Acid,S-Adenosylmethionine, 3-Amino-4-hydroxybutyric Acid, Amixetrine,Bendazac, Benzydamine, Bucolome, Difenpiramide, Ditazol, Emorfazone,Guaiazulene, Nabumetone, Nimesulide, Orgotein, Oxaceprol, Paranyline,Perisoxal, Pifoxime, Proquazone, Proxazole and Tenidap;

Antimalarial drugs such as Acedapsone, Amodiaquin, Arteether,Artemether, Artemisinin, Artesunate, Bebeerine, Berberine, Chirata,Chlorguanide, Chloroquine, Chlorproguanil, Cinchona, Cinchonidine,Cinchonine, Cycloguanil, Gentiopicrin, Halofantrine, Hydroxychloroquine,Mefloquine Hydrochloride, 3-Methylarsacetin, Pamaquine, Plasmocid,Primaquine, Pyrimethamine, Quinacrine, Quinine, Quinine Bisulfate,Quinine Carbonate, Quinine Dihydrobromide, Quinine Dihydrochloride,Quinine Ethylcarbonate, Quinine Formate, Quinine Gluconate, QuinineHydriodide, Quinine Hydrochloride, Quinine Salicylate, Quinine Sulfate,Quinine Tannate, Quinine Urea Hydrochloride, Quinocide, Quinoline andSodium Arsenate Diabasic;

Antimigraine drugs such as Alpiropride, Dihydroergotamine, Eletriptan,Ergocornine, Ergocorninine, Ergocryptine, Ergot, Ergotamine,Flumedroxone acetate, Fonazine, Lisuride, Methysergid(e), Naratriptan,Oxetorone, Pizotyline, Rizatriptan and Sumatriptan;

Antinauseant drugs such as Acetylleucine Monoethanolamine, Alizapride,Benzquinamide, Bietanautine, Bromopride, Buclizine, Chlorpromazine,Clebopride, Cyclizine, Dimenhydrinate, Diphenidol, Domperidone,Granisetron, Meclizine, Methalltal, Metoclopramide, Metopimazine,Nabilone, Ondansetron, Oxypendyl, Pipamazine, Piprinhydrinate,Prochlorperazine, Scopolamine, Tetrahydrocannabinols, Thiethylperazine,Thioproperzaine and Trimethobenzamide;

Antineoplastic drugs, including: Alkylating agents, such as Alkylsulfonates such as Busulfan, Improsulfan and Piposulfan;

Aziridines such as Benzodepa, Carboquone, Meturedepa and Uredepa;

Ethylenimines and methylmelamines such as Altretamine,Triethylenemelamine, Triethylenephosphoramide,Triethylenethiophosphoramide and Trimethylolomelamine;

Nitrogen mustards such as Chlorambucil, Chlornaphazine,Cyclophosphamide, Estramustine, Ifosfamide, Mechlorethamine,Mechlorethamine Oxide Hydrochloride, Melphalan, Novembichin,Phenesterine, Prednimustine, Trofosfamide and Uracil Mustard;

Nitrosoureas such as Carmustine, Chlorozotocin, Fotemustine, Lomustine,Nimustine and Ranimustine; and

others such as Camptothecin, Dacarbazine, Mannomustine, Mitobronitol,Mitolactol and Pipobroman;

Antibiotics such as Aclacinomycins, Actinomycin F₁, Anthramycin,Azaserine, Bleomycins, Cactinomycin, Carubicin, Carzinophilin,Chromomycins, Dactinomycin, Daunorubicin, 6-Diazo-5-oxo-L-norleucine,Doxorubicin, Epirubicin, Mitomycins, Mycophenolic Acid, Nogalamycin,Olivomycins, Peplomycin, Plicamycin, Porfiromycin, Puromycin,Streptonigrin, Streptozocin, Tubercidin, Ubenimex, Zinostatin andZorubicin;

Antimetabolites, including: Folic acid analogs such as Denopterin,Methotrexate, Pteropterin and Trimetrexate;

Purine analogs such as Fludarabine, 6-Mercaptopurine, Thiamiprine andThioguanine; and

Pyrimidine analogs such as Ancitabine, Azacitidine, 6-Azauridine,Carmofur, Cytarabine, Doxifluridine, Enocitabine, FloxuridineFluorouracil and Tegafur;

Enzymes such as L-Asparaginase; and

others such as Aceglatone, Amsacrine, Bestrabucil, Bisantrene,Bryostatin 1, Carboplatin, Cisplatin, Defosfamide, Demecolcine,Diaziquone, Eflornithine, Elliptinium Acetate, Etoglucid, Etoposide,Gallium Nitrate, Hydroxyurea, Interferon-α, Interferon-β, Interferon-γ,Interleukin-2, Lentinan, Letrozole, Lonidamine, Mitoguazone,Mitoxantrone, Mopidamol, Nitracrine, Pentostatin, Phenamet, Pirarubicin,Podophyllinic Acid, 2-Ethylhydrazide, Polynitrocubanes, Procarbazine,PSK7, Razoxane, Sizofuran, Spirogermanium, Taxol, Teniposide, TenuazonicAcid, Triaziquone, 2.2′.2″-Trichlorotriethylamine, Urethan, Vinblastine,Vincristine, Vindesine and Vinorelbine;

Antineoplastic (hormonal) drugs, including: Androgens such asCalusterone, Dromostanolone Propionate, Epitiostanol, Mepitiostane andTestolactone;

Antiadrenals such as Aminoglutethimide, Mitotane and Trilostane;

Antiandrogens such as Flutamide and Nilutamide; and

Antiestrogens such as Tamoxifen and Toremifene;

Antineoplastic adjuncts including folic acid replenishers such asFrolinic Acid;

Antiparkinsonian drugs such as Amantadine, Benserazide, Bietanautine,Biperiden, Bromocriptine, Budipine, Cabergoline, Carbidopa, Deprenyl(a/k/a L-deprenyl, L-deprenil, L-deprenaline and selegiline),Dexetimide, Diethazine, Diphenhydramine, Droxidopa, Ethopropazine,Ethylbenzhydramine, Levodopa, Naxagolide, Pergolide, Piroheptine,Pramipexole, Pridinol, Prodipine, Quinpirole, Remacemide, Ropinirole,Terguride, Tigloidine and Trihexyphenidyl Hydrochloride;

Antipheochromocytoma drugs such as Metyrosine, Phenoxybenzamine andPhentolamine;

Antipneumocystis drugs such as Eflornithine, Pentamidine andSulfamethoxazole;

Antiprostatic hypertrophydrugs such as Gestonorone Caproate,Mepartricin, Oxendolone and Proscar;

Antiprotozoal drugs (Leishmania) such as Antimony Sodium Gluconate,Ethylstibamine, Hydroxystilbamidine, N-Methylglucamine, Pentamidine,Stilbamidine and Urea Stibamine;

Antiprotozoal drugs (Trichomonas) such as Acetarsone, Aminitrozole,Anisomycin, Azanidazole, Forminitrazole, Furazolidone, Hachimycin,Lauroguadine, Mepartricin, Metronidazole, Nifuratel, Nifuroxime,Nimorazole, Secnidazole, Silver Picrate, Tenonitrozole and Timidazole;

Antiprotozoal drugs (Trypanosoma) such as Benznidazole, Eflornithine,Melarsoprol, Nifurtimox, Oxophenarsine, Hydrochloride, Pentamidine,Propamidine, Puromycin, Quinapyramine, Stilbamidine, Suramin Sodium,Trypan Red and Tryparasmide;

Antipuritics such as Camphor, Cyproheptadine, Dichlorisone, Glycine,Halometasone, 3-Hydroxycamphor, Menthol, Mesulphen, Methdilazine,Phenol, Polidocanol, Risocaine, Spirit of Camphor, Thenaldine,Tolpropamine and Trimeprazine;

Antipsoriatic drugs such as Acitretin, Ammonium Salicylate, Anthralin,6-Azauridine, Bergapten(e), Chrysarobin, Etretinate and Pyrogallol;

Antipsychotic drugs, including: Butyrophenones such as Benperidol,Bromperidol, properidol, Fluanisone, Haloperidol, Melperone, Moperone,Pipamperone, Spiperone, Timiperone and Trifluperidol;

Phenothiazines such as Acetophenazine, Butaperazine, Carphenazine,Chlorproethazine, Chlorpromazine, Clospirazine, Cyamemazine, Dixyrazine,Fluphenazine, Imiclopazine, Mepazine, Mesoridazine, Methoxypromazine,Metofenazate, Oxaflumazine, Perazine, Pericyazine, Perimethazine,Perphenazine, Piperacetazine, Pipotiazine, Prochlorperazine, Promazine,Sulforidazine, Thiopropazate, Thioridazine, Trifluoperazine andTriflupromazine;

Thioxanthenes such as Chlorprothixene, Clopenthixol, Flupentixol andThiothixene;

other tricyclics such as Benzquinamide, Carpipramine, Clocapramine,Clomacran, Clothiapine, Clozapine, Opipramol, Prothipendyl,Tetrabenazine, and Zotepine; and

others such as Alizapride, Amisulpride, Buramate, Fluspirilene,Molindone, Penfluridol, Pimozide, Spirilene and Sulpiride;

Antipyretics such as Acetaminophen, Acetaminosalol, Acetanilide,Aconine, Aconite, Aconitine, Alclofenac, Aluminum Bis(acetylsalicylate),Aminochlorthenoxazin, Aminopyrine, Aspirin, Benorylate, Benzydamine,Berberine, p-Bromoacetanilide, Bufexamac, Bumadizon, CalciumAcetylsalicylate, Chlorthenoxazin(e), Choline Salicylate, Clidanac,Dihydroxyaluminum Acetylsalicylate, Dipyrocetyl, Dipyrone, Epirizole,Etersalate, Imidazole Salicylate, Indomethacin, Isofezolac,p-Lactophenetide, Lysine Acetylsalicylate, Magnesium Acetylsalicylate,Meclofenamic Acid, Morazone, Morpholine Salicylate, Naproxen,Nifenazone, 51-Nitro-2′-propoxyacetanilide, Phenacetin, Phenicarbazide,Phenocoll, Phenopyrazone, Phenyl Acetylsalicylate, Phenyl Salicylate,Pipebuzone, Propacetamol, Propyphenazone, Ramifenazone, Salacetamide,Salicylamide O-Acetic Acid, Sodium Salicylate, Sulfamipyrine,Tetrandrine and Tinoridine;

Antirickettsial drugs such as p-Aminobenzoic Acid, Chloramphenicol,Chloramphenicol Palmitate, Chloramphenicol Pantothenate andTetracycline;

Antiseborrheic drugs such as Chloroxine, 3-O-Lauroylpyridoxol Diacetate,Piroctone, Pyrithione, Resorcinol, Selenium Sulfides and Tioxolone;

Antiseptics, including: Guanidines such as Alexidine, Ambazone,Chlorhexidine and Picloxydine;

Halogens and halogen compounds such as Bismuth Iodide Oxide, BismuthIodosubgallate, Bismuth Tribromophenate, Bornyl Chloride, CalciumIodate, Chlorinated Lime, Cloflucarban, Fluorosalan, Iodic Acid, Iodine,Iodine Monochloride, Iodine Trichloride, Iodoform, MethenamineTetraiodine, Oxychlorosene, Povidone-Iodine, Sodium Hypochlorite, SodiumIodate, Symclosene, Thymol Iodide, Triclocarban, Triclosan andTroclosene Potassium;

Mercurial compounds such as Hydrargaphen, Meralein Sodium, Merbromin,Mercuric Chloride, Mercuric Chloride, Ammoniated, Mercuric Sodiump-Phenol-sulfonate, Mercuric Succinimide, Mercuric Sulfide, Red,Mercurophen, Mercurous Acetate, Mercurous Chloride, Mercurous Iodide,Nitromersol, Potassium Tetraiodo-mercurate(II), PotassiumTriiodomercurate (II) Solution, Thimerfonate Sodium and Thimerosal;

Nitrofurans such as Furazolidone, 2-(Methoxymethyl)-5-nitrofuran,Nidroxyzone, Nifuroxime, Nifurzide and Nitrofurazone;

Phenols such as Acetomeroctol, Bithionol, Cadmium Salicylate, Carvacrol,Chloroxylenol, Clorophene, Cresote, Cresol(s), p-Cresol, Fenticlor,Hexachlorophene, 1-Naphthyl Salicylate, 2-Naphthyl Salicylate,2,4,6-Tribromo-m-cresol, and 3′,4′,5′-Trichlorosalicylanilide;

Quinolines such as Aminoquinuride, Benzoxiquine, Broxyquinoline,Chloroxine, Chlorquinaldol, Cloxyquin, Ethylhydrocupreine, Euprocin,Halquinol, Hydrastine, 8-Hydroxyquinoline, 8-Hydroxyquinoline Sulfateand Iodochlorhydroxyquin; and

others such as Aluminum Acetate Solution, Aluminum Subacetate Solution,Aluminum Sulfate, 3-Amino-4-hydroxybutyric Acid, Boric Acid,Chlorhexidine, Chloroazodin, m-Cresyl Acetate, Cupric Sulfate,Dibromopropamidine, Ichthammol, Negatol, Noxytiolin, Ornidazole,β-Propiolactone, α-Terpineol;

Antispasmodic drugs such as Alibendol, Ambucetamide, Aminopromazine,Apoatropine, Bevonium Methyl Sulfate, Bietamiverine, Butaverine,Butropium Bromide, N-Butylscopolammonium Bromide, Caroverine,Cimetropium Bromide, Cinnamedrine, Clebopride, Coniine Hydrobromide,Coniine Hydrochloride, Cyclonium Iodide, Difemerine, Diisopromine,Dioxaphetyl Butyrate, Diponium Bromide, Drofenine, Emepronium Bromide,Ethaverine, Feclemine, Fenalamide, Fenoverine, Fenpiprane, FenpiveriniumBromide, Fentonium Bromide, Flavoxate, Flopropione, Gluconic Acid,Guaiactamine, Hydramitrazine, Hymecromone, Leiopyrrole, Mebeverine,Moxaverine, Nafiverine, Octamylamine, Octaverine, Pentapiperide,Phenamacide Hydrochloride, Phloroglucinol, Pinaverium Bromide,Piperilate, Pipoxolan Hydrochloride, Pramiverin, Prifinium Bromide,Properidine, Propivane, Propyromazine, Prozapine, Racefemine,Rociverine, Spasmolytol, Stilonium Iodide, Sultroponium, TiemoniumIodide, Tiquizium Bromide, Tiropramide, Trepibutone, Tricromyl,Trifolium, Trimebutine, N,N-Dimethyl-3,3-diphenyl-propylamine,Tropenzile, Trospium Chloride and Xenytropium Bromide;

Antithrombotic drugs such as Anagrelide, Argatroban, Cilostazol,Chrysoptin, Daltroban, Defibrotide, Enoxaparin, Fraxiparine, Indobufen,Lamoparan, Ozagrel, Picotamide, Plafibride, Reviparin, Tedelparin,Ticlopidine, Triflusal and Warfarin;

Antitussive drugs such as Alloclamide, Amicibone, Benproperine,Benzonatate, Bibenzonium Bromide, Bromoform, Butamirate, Butethamate,Caramiphen Ethanedisulfonate, Carbetapentane, Chlophedianol, Clobutinol,Cloperastine, Codeine, Codeine Methyl Bromide, Codeine N-Oxide, CodeinePhosphate, Codeine Sulfate, Cyclexanone, Dextromethorphan, DibunateSodium, Dihydrocodeine, Dihydrocodeinone Enol Acetate, Dimemorfan,Dimethoxanate, α,α-Diphenyl-2-piperidinepropanol, propropizine,Drotebanol, Eprazinone, Ethyl Dibunate, Ethylmorphine, Fominoben,Guaiapate, Hydrocodone, Isoaminile, Levopropoxyphene, Morclofone,Narceine, Normethadone, Noscapine, Oxeladin, Oxolamine, Pholcodine,Picoperine, Pipazethate, Piperidione, Prenoxdiazine Hydrochloride,Racemethorphan, Taziprinone Hydrochloride, Tipepidine and Zipeprol;

Antiulcerative drugs such as Aceglutamide Aluminum Complex,ε-Acetamido-caproic Acid Zinc Salt, Acetoxolone, Arbaprostil, BenexateHydrochloride, Bismuth Subcitrate Sol (Dried), Carbenoxolone, Cetraxate,Cimetidine, Enprostil, Esaprazole, Famotidine, Ftaxilide, Gefarnate,Guaiazulene, Irsogladine, Misoprostol, Nizatidine, Omeprazole,Ornoprostil, γ-Oryzanol, Pifamine, Pirenzepine, Plaunotol, Ranitidine,Rioprostil, Rosaprostol, Rotraxate, Roxatidine Acetate, Sofalcone,Spizofurone, Sucralfate, Teprenone, Trimoprostil, Trithiozine, Troxipideand Zolimidine;

Antiurolithic drugs such as Acetohydroxamic Acid, Allopurinol, PotassiumCitrate and Succinimide;

Antivenin drugs such as Lyovac antivenin;

Antiviral drugs, including: Purines and pyrimidinones such as Acyclovir,Cytarabine, Dideoxyadenosine, Dideoxycytidine, Dideoxyinosine,Edoxudine, Floxuridine, Ganciclovir, Idoxuridine, Inosine Pranobex,MADU, Penciclovir, Trifluridine, Vidarabine and Zidovudine; and

others such as Acetylleucine Monoethanolamine, Amantadine, Amidinomycin,Cosalane, Cuminaldehyde Thiosemicarbazone, Foscarnet Sodium, Imiquimod,Interferon-α, Interferon-β, Interferon-γ, Kethoxal, Lysozyme,Methisazone, Moroxydine, Podophyllotoxin, Ribavirin, Rimantadine,Stallimycin, Statolon, Tromantadine and Xenazoic Acid;

Anxiolytic drugs, including: Arylpiperazines such as Buspirone,Gepirone, Ipsapirone and Tandospirone;

Benzodiazepine derivatives such as Alprazolam, Bromazepam, Camazepam,Chlordiazepoxide, Clobazam, Clorazepate, Clotiazepam, Cloxazolam,Diazepam, Ethyl Loflazepate, Etizolam, Fludiazepam, Flutazolam,Flutoprazepam, Halazepam, Ketazolam, Lorazepam, Loxapine, Medazepam,Metaclazepam, Mexazolam, Nordazepam, Oxazepam, Oxazolam, Pinazepam,Prazepam and Tofisopam;

Carbamates such as Cyclarbamate, Emylcamate, Hydroxyphenamate,Meprobamate, Phenprobamate and Tybamate; and

others such as Alpidem, Benzoctamine, Captodiamine, Chlormezanone,Etifoxine, Flesinoxan, Fluoresone, Glutamic Acid, Hydroxyzine,Lesopitron, Mecloralurea, Mephenoxalone, Mirtazapine, Oxanamide,Phenaglycodol, Suriclone and Zatosetron;

Benzodiazepine antagonists such as Flumazenil;

Bronchodilators, including: Ephedrine derivatives such as Albuterol,Bambuterol, Bitolterol, Carbuterol, Clenbuterol, Clorprenaline,Dioxethedrin, Ephedrine, Epinephrine, Eprozinol, Etafedrine,Ethylnorepinephrine, Fenoterol, Hexoprenaline, Isoetharine,Isoproterenol, Mabuterol, Metaproterenol, N-Methylephedrine, Pirbuterol,Procaterol, Protokylol, Reproterol, Rimiterol, Salmeterol, Soterenol,Terbutaline and Tulobuterol;

Quaternary ammonium compounds such as Bevonium Methyl Sulfate,Clutropium Bromide, Ipratropium Bromide and Oxitropium Bromide;

Xanthine derivatives such as Acefylline, Acefylline piperazine,Ambuphylline, Aminophylline, Bamifylline, choline Theophyllinate,Doxofylline, Dyphylline, Enprofylline, Etamiphyllin, Etofylline,Guaithylline, Proxyphylline, Theobromine, 1-Theobromineacetic Acid andTheophylline; and

others such as Fenspiride, Medibazine, Montelukast, Methoxyphenamine,Tretoquinol and Zafirlukast;

Calcium channel blockers, including: Arylalkylamines such as Bepridil,Ditiazem, Fendiline, Gallopamil, Prenylamine, Terodiline and Verapamil;

Dihydropyridine derivatives such as Felodipine, Isradipine, Nicardipine,Nifedipine, Nilvadipine, Nimodipine, Nisoldipine and Nitrendipine;

piperazine derivatives such as Cinnarizine, Flunarizine and Lidoflazine;and

others such as Bencyclane, Etafenone and Perhexyline;

Calcium regulators such as Calcifediol, Calcitonin, Calcitriol,Clodronic Acid, Dihydrotachysterol, Elcatonin, Etidronic Acid,Ipriflavone, Pamidronic Acid, Parathyroid Hormone and TeriparatideAcetate;

Cardiotonics such as Acefylline, Acetyldigititoxins, 2-Amino-4-picoline,Amrinone, Benfurodil Hemisuccinate, Buclasdesine, Cerberoside,Camphotamide, Convallatoxin, Cymarin, Denopamine, Deslanoside, Ditalin,Digitalis, Digitoxin, Digoxin, Dobutamine, Dopamine, Dopexamine,Enoximone, Erythrophleine, Fenalcomine, Gitalin, Gitoxin, Glycocyamine,Heptaminol, Hydrastinine, Ibopamine, Lanotodises, Metamivam, Milrinone,Neriifolin, Oleandrin, Ouabain, Oxyfedrine, Prenalterol, Proscillaridin,Resibufogenin, Scillaren, Scillarenin, Strophanthin, Sulmazole,Theobromine and Xamoterol;

Chelating agents such as Deferoxamine, Ditiocarb Sodium, Edetate CalciumDisodium, Edetate Disodium, Edetate Sodium, Edetate Trisodium,Penicillamine, Pentetate Calcium Trisodium, Pentetic Acid, Succimer andTrientine;

Cholecystokinin antagonists such as Proglumide;

Cholelitholytic agents such as Chenodiol, Methyl tert-Butyl Ether,Monooctanoin and Ursodiol;

Choleretics such as Alibendol, Anethole Trithione, Azintamide, CholicAcid, Cicrotoic Acid, Clanobutin, Cyclobutyrol, Cyclovalone, Cynarin(e),Dehydrocholic Acid, Deoxycholic Acid, Dimecrotic Acid, α-EthylbenzylAlcohol, Exiproben, Febuprol, Fencibutirol, Fenipentol, Florantyrone,Hymecromone, Menbutone, 3-(o-Methoxyphenyl)-2-phenylacrylic Acid,Metochalcone, Moquizone, Osalmid, Ox Bile Extract, 4.4′-Oxydi-2-butanol,Piprozolin, Prozapine, 4-Salicyloylmorpholine, Sincalide, TaurocholicAcid, Timonacic, Tocamphyl, Trepibutone and Vanitiolide;

Cholinergic agents such as Aceclidine, Acetylcholine Bromide,Acetylcholide Chloride, Aclatonium Napadisilate, Benzpyrinium Bromide,Bethanechol chloride, Carbachol, Carpronium chloride, DemecariumBromide, Dexpanthenol, Diisopropyl Paraoxon, Echothiophate Iodide,Edrophonium chloride, Eseridine, Furtrethonium, Isofluorophate,Methacholine chloride, Muscarine, Neostigmine, Oxapropanium Iodide,Physostigmine and Pyridostigmine Bromide;

Cholinesterase inhibitors such as Ambenonium Chloride, DistigmineBromide and Galanthamine;

Cholinesterase reactivators such as Obidoxime Chloride and PralidoximeChloride;

Central nervous system stimulants and agents such as Amineptine,Amphetimine, Amphetaminil, Bemegride, Benzphetamine, Brucine, Caffeine,Chlorphentermine, Clofenciclan, Clortermine, Coca, Demanyl Phosphate,Dexoxadrol, Dextroamphetamine Sulfate, Diethylpropion,N-Ethylamphetamine, Ethamivan, Etifelmin, Etryptamine, Fencamfamine,Fenethylline, Fenozolone, Fluorothyl, Galanthamine, HexacyclonateSodium, Homocamfin, Mazindol, Mefexamide, Methamphetamine,Methylphenidate, Nikethamide, Pemoline, Pentylenetetrazole,Phendimetrazine, Phenmetrazine, Phentermine, Picrotoxin, Pipradrol,Prolintane and Pyrovalerone;

Decongestants such as Amidephrine, Cafaminol, Cyclopentamine, Ephedrine,Epinephrine, Fenoxazoline, Indanazoline, Metizoline, Naphazoline,Nordefrin Hydrochloride, Octodrine, oxymetazoline, PhenylephrineHydrochloride, Phenylpropanolamine Hydrochloride,Phenylpropylmethylamine, Propylhexedrine, Pseudoephedrine,Tetrahydrozoline, Tymazoline and Xylometazoline;

Dental agents, including: Bisphosphonates (anti-periodontal disease andbone resorption) such as Alendronate, Clodronate, Etidronate,Pamidronate and Tiludronate; Carries Prophylactics such as Arginine andSodium Fluoride;

Desensitizing Agents such as Potassium Nitrate and Citrate Oxalate;

Depigmentors such as Hydroquinine, Hydroquinone and Monobenzone;

Diuretics, including: Organomercurials such as Chlormerodrin,Meralluride, Mercamphamide, Mercaptomerin Sodium, Mercumallylic Acid,Mercumatilin Sodium, Mercurous Chloride and Mersalyl;

Pteridines such as Furterene and Triamterene;

Purines such as Acefylline, 7-Morpholinomethyltheophylline, Pamabrom,Protheobromine and Theobromine;

Steroids such as Canrenone, Oleandrin and Spironolactone;

Sulfonamide derivatives such as Acetazolamide, Ambuside, Azosemide,Bumetanide, Butazolamide, Chloraminophenamide, Clofenamide, Clopamide,Clorexolone, Diphenylmethane-4.4°-disulfonamide, Disulfamide,Ethoxzolamide, Furosemide, Indapamide, Mefruside, Methazolamide,Piretanide, Quinethazone, Torasemide, Tripamide and Xipamide;

Uracils such as Aminometradine and Amisometradine;

others such as Amanozine, Amiloride, Arbutin, Chlorazanil, EthacrynicAcid, Etozolin, Hydracarbazine, Isosorbide, Mannitol, Metochalcone,Muzolimine, Perhexyline, Ticrynafen and Urea;

Dopamine receptor agonists such as Bromocriptine, Dopexamine,Fenoldopam, Ibopamine, Lisuride, Naxagolide and Pergolide;

Ectoparasiticides such as Amitraz, Benzyl Benzoate, Carbaryl,Crotamiton, DDT, Dixanthogen, Isobornyl Thiocyanoacetate—Technical, LimeSulfurated Solution, Lindane, Malathion, Mercuric Oleate, Mesulphen andSulphur—Pharmaceutical;

Enzymes, including: Digestive enzymes such as α-Amylase (SwinePancreas), Lipase, Pancrelipase, Pepsin and Rennin;

Mucolytic enzymes such as Lysozyme;

Penicillin inactivating enzymes such as Penicillinase; and

Proteolytic enzymes such as Collagenase, Chymopapain, Chymotrypsins,Papain and Trypsin;

Enzyme inducers (hepatic) such as Flumecinol;

Estrogens, including: Nonsteroidal estrogens such as Benzestrol,Broparestrol, Chlorotrianisene, Dienestrol, Diethylstilbestrol,Diethylstilbestrol Diproprionate, Dimestrol, Fosfestrol, Hexestrol,Methallenestril and Methestrol; and

Steroidal estrogens such as Colpormon, Conjugated Estrogenic Hormones,Equilenin, Equilin, Estradiol, Estradiol Benzoate, Estradiol17β-Cypionate, Estriol, Estrone, Ethinyl Estradiol, Mestranol,Moxestrol, Mytatrienediol, Quinestradiol and Quinestrol;

Gastric secretion inhibitors such as Enterogastrone and Octreotide;

Glucocorticoids such as 21-Acetoxypregnenolone, Alclometasone,Algestone, Amicinonide, Beclomethasone, Betamethasone, Budesonide,Chloroprednisone, Clobetasol, Blovetasone, Clocortolone, Cloprednol,Corticosterone, Cortisone, Cortivazol, Deflazacort, Desonide,Desoximetasone, Dexamethasone, Diflorasone, Diflucortolone,Difluprednate, Enoxolone, Fluazacort, Flucloronide, Flumethasone,Flunisolide, Fluocinolone Acetonide, Fluocinonide, Fluocortin Butyl,Fluocortolone, Fluorometholone, Fluperolone Acetate, FluprednideneAcetate, Fluprednisolone, Flurandrenolide, Formocortal, Halcinonide,Halometasone, Halopredone Acetate, Hydrocortamate, Hydrocortisone,Hydrocortisone Acetate, Hydrocortisone Phosphate, Hydrocortisone21-Sodium Succinate, Hydrocortisone Tebutate, Mazipredone, Medrysone,Meprednisone, Methylprednisolone, Mometasone Furoate, Paramethasone,Prednicarbate, Prednisolone, Prednisolone 21-Diethylaminoacetate,Prednisone Sodium Phosphate, Prednisolone Sodium Succinate, PrednisoloneSodium 21-m-Sulfobenzoate, Prednisolone 21-Stearoylglycolate,Prednisolone Tebutate, Prednisolone 21-Trimethylacetate, Prednisone,Prednival, Prednylidene, Prednylidene 21-Diethylaminoacetate,Tixocortol, Triamcinolone, Triamcinolone Acetonide, TriamcinoloneBenetonide and Triamcinolone Hexacetonide;

Gonad-Stimulating principles such as Buserelin, Clomiphene, Cyclofenil,Epimestrol, FSH, HCG and LH-RH;

Gonadotropic hormones such as LH and PMSG;

Growth hormone inhibitors such as Octreotide and Somatostatin;

Growth hormone releasing factors such as Sermorelin;

Growth stimulants such as Somatotropin;

Hemolytic agents such as Phenylhydrazine and PhenylhydrazineHydrochloride;

Heparin antagonists such as Hexadimethrine Bromide and Protamines;

Hepatoprotectants such as S-Adenosylmethionine, Betaine, Catechin,Citiolone, Malotilate, Orazamide, Phosphorylcholine, Protoporphyrin IX,Silymarin-Group, Thioctic Acid and Tiopronin;

Immunomodulators such as Amiprilose, Bucillamine, Ditiocarb Sodium,Inosine Pranobex, Interferon-y, Interleukin-2, Lentinan, Muroctasin,Platonin, Procodazole, Tetramisole, Thymomodulin, Thymopentin andUbenimex;

Immunosuppressants such as Azathioprine, Cyclosporins and Mizoribine;

Ion exchange resins such as Carbacrylic Resins, Cholestyramine Resin,Colestipol, Polidexide, Resodec and Sodium Polystyrene Sulfonate;

Lactation stimulating hormone such as Prolactin;

LH-RH agonists such as Buserelin, Goserelin, Leuprolide, Nafarelin, andTriptorelin;

Lipotropic agents such as N-Acetylmethionine, Choline Chloride, CholineDehydrocholate, Choline Dihydrogen Citrate, Inositol, Lecithin andMethionine;

Lupus erythematosus suppressants such as Bismuth Sodium Triglycollamate,Bismuth Subsalicylate, Chloroquine and Hydroxychloroquine;

Mineralocorticoids such as Aldosterone, Deoxycorticosterone,Deoxycorticosterone Acetate and Fludrocortisone;

Miotic drugs such as Carbachol, Physostigmine, Pilocarpine andPilocarpus;

Monoamine oxidase inhibitors such as Deprenyl, Iproclozide, Iproniazid,Isocarboxazid, Moclobemide, Octamoxin, Pargyline, Phenelzine,Phenoxypropazine, Pivalylbenzhydrazine, Prodipine, Toloxatone andTranylcypromine;

Mucolytic agents such as Acetylcysteine, Bromhexine, Carbocysteine,Domiodol, Letosteine, Lysozyme, Mecysteine Hydrochloride, Mesna,Sobrerol, Stepronin, Tiopronin and Tyloxapol;

Muscle relaxants (skeletal) such as Afloqualone, Alcuronium, AtracuriumBesylate, Baclofen, Benzoctamine, Benzoquinonium Chloride,C-Calebassine, Carisoprodol, Chlormezanone, Chlorphenesin Carbamate,Chlorproethazine, Chlorzoxazone, Curare, Cyclarbamate, Cyclobenzaprine,Dantrolene, Decamethonium Bromide, Diazepam, Eperisone, FazadiniumBromide, Flumetramide, Gallamine Triethiodide, Hexacarbacholine Bromide,Hexafluorenium Bromide, Idrocilamide, Laudexium Methyl Sulfate,Leptodactyline, Memantine, Mephenesin, Mephenoxalone, Metaxalone,Methocarbamol, Metocurine Iodide, Nimetazepam, Orphenadrine, PancuroniumBromide, Phenprobamate, Phenyramidol, Pipecurium Bromide, Promoxolane,Quinine Sulfate, Styramate, Succinylcholine Bromide, SuccinylcholineChloride, Succinylcholine Iodine, Suxethonium Bromide, Tetrazepam,Thiocolchicoside, Tizanidine, Tolperisone, Tubocurarine Chloride,Vecuronium Bromide and Zoxolamine;

Narcotic antagonists such as Amiphenazole, Cyclazocine, Levallorphan,Nadide, Nalmefene, Nalorphine, Nalorphine Dinicotinate, Naloxone andNaltrexone;

Neuroprotective agents such as Dizocilpine;

Nootropic agents such as Aceglutamide, Acetylcarnitine, Aniracetam,Bifematlane, Exifone, Fipexide, Idebenone, Indeloxazine Hydrochloride,Nizofenone, Oxiracetam, Piracetam, Propentofylline, Pyritinol andTacrine;

Ophthalmic agents such as 15-ketoprostaglandins;

Ovarian hormone such as Relaxin;

Oxytocic drugs such as Carboprost, Cargutocin, Deaminooxytocin,Ergonovine, Gemeprost, Methylergonovine, Oxytocin, Pituitary(Posterior), Prostaglandin E₂, Prostaglandin F_(2a) and Sparteine;

Pepsin inhibitors such as Sodium Amylosulfate;

Peristaltic stimulants such as Cisapride;

Progestogens such as Allylestrenol, Anagestone, Chlormadinone Acetate,Delmadinone Acetate, Demegestone, Desogestrel, Dimethisterone,Dydrogesterone, Ethisterone, Ethynodiol, Fluorogestone Acetate,Gestodene, Gestonorone Caproate, Haloprogesterone,17-Hydroxy-16-methylene-progesterone, 17α-Hydroxyprogesterone,17α-Hydroxyprogesterone Caproate, Lynestrenol, Medrogestone,Medroxyprogesterone, Megestrol Acetate, Melengestrol, Norethindrone,Norethynodrel, Norgesterone, Norgestimate, Norgestrel, Norgestrienone,Norvinisterone, Pentagestrone, Progesterone, Promegestone, Quingestroneand Trengestone;

Prolactin inhibitors such as Metergoline;

Prostaglandins and prostaglandin analogs such as Arbaprostil,Carboprost, Enprostil, Gemeprost, Limaprost, Misoprostol, Ornoprostil,Prostacyclin, Prostaglandin E₁, Prostaglandin E₂, Prostaglandin F_(2a),Rioprostil, Rosaprostol, Sulprostone and Trimoprostil;

Protease inhibitors such as Aprotinin, Camostat, Gabexate andNafamostat;

Respiratory stimulants such as Almitrine, Bemegride, Carbon Dioxide,Cropropamide, Crotethamide, Dimefline, Dimorpholamine, Doxapram,Ethamivan, Fominoben, Lobeline, Mepixanox, Metamivam, Nikethamide,Picrotoxin, Pimeclone, Pyridofylline, Sodium Succinate and Tacrine;

Sclerosing agents such as Ethanolamine, Ethylamine, 2-Hexyl-decanoicAcid, Polidocanol, Quinine Bisulfate, Quinine Urea Hydrochloride, SodiumRicinoleate, Sodium Tetradecyl Sulfate and Tribenoside;

Sedatives and hypnotics, including: Acyclic ureides such asAcecarbromal, Apronalide, Bromisovalum, Capuride, Carbromal andEctylurea;

Alcohols such as Chlorhexadol, Ethchlorvynol, Meparfynol,4-Methyl-5-thiazoleethanol, tert-Pentyl Alcohol and2,2,2-Trichloroethanol;

Amides such as Butoctamide, Diethylbromoacetamide, Ibrotamide,Isovaleryl Diethylamide, Niaprazine, Tricetamide, Trimetozine, Zolpidemand Zopiclone;

Barbituric acid derivatives such as Allobarbital, Amobarbital,Aprobarbital, Barbital, Brallobarbital, Butabarbital Sodium, Butalbital,Butallylonal, Butethal, Carbubarb, Cyclobarbital, Cyclopentobarbital,Enallylpropymal, 5-Ethyl-5-(1-piperidyl) barbituric Acid,5-Furfuryl-5-isopropylbarbituric Acid, Heptabarbital, Hexethal Sodium,Hexobarbital, Mephobarbital, Methitural, Narcobarbital, Nealbarbital,Pentobarbital Sodium, Phenallymal, Phenobarbital, Phenobarbital Sodium,Phenylmethylbarbituric Acid, Probarbital, Propallylonal, Proxibarbal,Reposal, Secobarbital Sodium, Talbutal, Tetrabarbital, VinbarbitalSodium and Vinylbital;

Benzodiazepine derivatives such as Brotizolam, Doxefazepam, Estazolam,Flunitrazepam, Flurazepam, Haloxazolam, Loprazolam, Lormetazepam,Nitrazepam, Quazepam, Temazepam and Triazolam;

Bromides such as Ammonium Bromide, Calcium Bromide, CalciumBromolactobionate, Lithium Bromide, Magnesium Bromide, Potassium Bromideand Sodium Bromide;

Carbamates such as Amyl Carbamate—Tertiary, Ethinamate, Hexapropymate,Meparfynol Carbamate, Novonal and Tricholorourethan;

Chloral derivatives such as Carbocloral, Chloral Betaine, ChloralFormamide, Chloral Hydrate, Chloralantipyrine, Dichloralphenazone,Pentaerythritol Chloral and Triclofos;

Piperidinediones such as Glutethimide, Methyprylon, Piperidione,Pyrithyldione, Taglutimide and Thalidomide;

Quinazolone derivatives such as Etaqualone, Mecloqualone andMethaqualone; and

others such as Acetal, Acetophenone, Aldol, Ammonium Valerate,Amphenidone, d-Bornyl α-Bromoisovalerate, d-Bornyl Isovalerate,Bromoform, Calcium 2-Ethylbutanoate, Carfimate, α-Chloralose,Clomethiazole, Cypripedium, Doxylamine, Etodroxizine, Etomidate,Fenadiazole, Homofenazine, Hydrobromic Acid, Mecloxamine, MenthylValerate, Opium, Paraldehyde, Perlapine, Propiomazine, Rilmazafone,Sodium Oxybate, Sulfonethylmethane and Sulfonmethane;

Thrombolytic agents such as APSAC, Plasmin, Pro-Urokinase,Streptokinase, Tissue Plasminogen Activator and Urokinase;

Thyrotropic hormones such as TRH and TSH;

Uricosurics such as Benzbromarone, Ethebenecid, Orotic Acid,Oxycinchophen, Probenecid, Sulfinpyrazone, Ticrynafen and Zoxazolamine;

Vasodilators (cerebral) such as Bencyclane, Cinnarizine, Citicoline,Cyclandelate, Ciclonicate, Diisopropylamine Dichloroacetate,Eburnamonine, Fenoxedil, Flunarizine, Ibudilast, Ifenprodil, Nafronyl,Nicametate, Nicergoline, Nimodipine, Papaverine, Pentifylline,Tinofedrine, Vincamine, Vinpocetine and Viquidil;

Vasodilators (coronary) such as Amotriphene, Bendazol, BenfurodilHemisuccinate, Benziodarone, Chloacizine, Chromonar, Clobenfurol,Clonitrate, Dilazep, Dipyridamole, proprenilamine, Efloxate, Erythritol,Erythrityl Tetranitrate, Etafenone, Fendiline, Floredil, Ganglefene,Hexestrol Bis(β-diethylaminoethyl ether), Hexobendine, Itramin Tosylate,Khellin, Lidoflazine, Mannitol Hexanitrate, Medibazine, Nicorandil,Nitroglycerin, Pentaerythritol Tetranitrate, Pentrinitrol, Perhexyline,Pimethylline, Prenylamine, Propatyl Nitrate, Pyridofylline, Trapidil,Tricromyl, Trimetazidine, TroInitrate Phosphate and Visnadine;

Vasodilators (peripheral) such as Aluminum Nicotinate, Bamethan,Bencyclane, Betahistine, Bradykinin, Brovincamine, Bufeniode,Buflomedil, Butalamine, Cetiedil, Ciclonicate, Cinepazide, Cinnarizine,Cyclandelate, Diisopropylamine Dichloroacetate, Eledoisin, Fenoxedil,Flunarizine, Hepronicate, Ifenprodil, Inositol Niacinate, Isoxsuprine,Kallidin, Kallikrein, Moxisylyte, Nafronyl, Nicametate, Nicergoline,Nicofuranose, Nicotinyl Alcohol, Nylidrin, Pentifylline, Pentoxifylline,Piribedil, Prostaglandin E₁, Suloctidil and Xanthinol Niacinate;

Vasoprotectants such as Benzarone, Bioflavonoids, Chromocarb,Clobenoside, Diosmin, Dobesilate Calcium, Escin, Folescutol,Leucocyanidin, Metescufylline, Quercetin, Rutin and Troxerutin;

Vitamins, vitamin sources, and vitamin extracts such as Vitamins A, B,C, D, E, and K and derivatives thereof, Calciferols, Glycyrrhiza andMecobalamin;

Vulnerary agents such as Acetylcysteine, Allantoin, Asiaticoside,Cadexomer Iodine, Chitin, Dextranomer and Oxaceprol;

Anticoagulants such as heparin; and

Miscellaneous such as Erythropoietin (Hematinic), Filgrastim,Finasteride (Benign Prostate Hypertrophy) and Interferon β1-α (MultipleSclerosis).

In certain embodiments, the agent to be delivered is one or moreproteins, hormones, vitamins or minerals. In certain embodiments, theagent to be delivered is selected from insulin, IGF-1, testosterone,vinpocetine, hexarelin, GHRP-6 or calcium. In certain embodiments, thecompositions contain two or more agents.

The above list of active agents is based upon those categories andspecies of drugs set forth on pages THER-1 to THER-28 of The MerckIndex, 12th Edition, Merck & Co. Rahway, N.J. (1996). This reference isincorporated by reference in its entirety.

IV. Polymers

The compositions optionally contain one or more polymers that modify theviscosity of the composition. The polymer used can coat theliposome/micelle/proteins to keep the solution from degrading until itreaches the site of absorption, such as the mucosal lining. In certainembodiments, the polymers for use herein are selected from homopolymerssuch as polyolefins including polyethylene, polypropylene, polybutene,and polymers of higher alpha-olefins; styrenic polymers includingpolystyrene, polymers made from styrene monomers with pendant alkylgroups such as poly(alpha-methylstyrene) and poly(para-methyl styrene),and halogenated versions of the above styrenic polymers; polydienesincluding polybutadiene, polyisoprene, and other polymers made fromalkylated diene monomers; polyamides; polyimides; polycarbonates;polyisobutylene; acrylics such as poly(methyl methacrylate), poly(butylmethacrylate), poly(acrylic acid); silicones such as poly(dimethylsiloxane) and the like; polysulfones; vinyl polymers such as poly(vinylchloride), poly(vinyl fluoride), poly(vinyl alcohol), poly(vinylphenol), poly(vinylidene chloride), poly(vinylidene fluoride),poly(tetrafluoro ethylene), poly(acrylonitrile), and the like;polyesters including poly(ethylene glycol) esters, poly(ethyleneterephthalate), poly(butylene terephthalate), and the like; polyethersincluding poly(ethylene oxide), poly(propyleneoxide),poly(oxymethylene), and the like; poly(phenylene oxide); poly(phenylenesulfide); poly(acrylates); poly(benzimidazoles) and the like; and otherpolymers made from polymerizable monomers; statistical copolymers of themonomers or repeat units described above including for examplecopolymers of ethylene with other monomers such as alpha-olefinsincluding propylene, butene-1, hexene, octene, and the like; dienes;vinyl acetate; vinyl alcohol; vinyl chloride; vinylidene chloride;copolymers of isobutylene with other monomers including isoprene,butadiene, para methylstyrene, styrene, and the like; copolymers ofstyrene with other monomers including butadiene, isoprene, maleicanhydride, acrylonitrile, oxazoline, and the like; copolymers ofbutadiene with other monomers including acrylonitrile; copolymers ofpropylene with other monomers including ethylene, butene, hexane,dienes, and the like; block copolymers made from units of any of theabove homopolymers or copolymers including styrene-diene block polymerssuch as styrene-isoprene-styrene triblock copolymer,styrene-butadiene-styrene triblock copolymers,styrene-ethylene/propylene-styrene triblock copolymers (all ratios ofethylene to propylene), and the like; graft copolymers made from unitsof any of the above homopolymers or copolymers includingpoly(ethylene-graft-propylene), poly(styrene-graft-butadiene) and thelike; and derivatized versions of any of the above homopolymers orcopolymers including for example those made by sulfonation, amination,and carboxylation and the like, such as sulfonated polystyrene,sulfonated ethylene-propylene-diene monomer, and the like. The term“polymer” as used herein also includes combinations or mixtures of morethan one polymer wherein such combination or mixture exists in single ormultiphase blends.

Generally the identity and composition (i.e. the ratio or amount of eachtype of copolymer unit desired) of the copolymer can be varied dependingon the characteristics desired in the end product. It is within theskill of one ordinarily skilled in the art to make such selections.

In certain embodiments, the polymer for use herein is polyethyleneglycol ester. In certain embodiments, the polyethylene glycol ester isselected from PEG 200 monolaurate, PEG 200 dilaurate, PEG 300monolaurate, PEG 300 dilaurate, PEG 400 monolaurate, PEG 600 dilaurate,PEG 600 monolaurate, PEG 200 dilaurate, PEG 1000 monolaurate, PEG 1000dilaurate, PEG 1540 monolaurate, PEG 1540 dilaurate, PEG 4000monolaurate, PEG 4000 dilaurate, PEG 6000 monolaurate, PEG 6000dilaurate, PEG 200 monostearate, PEG 200 distearate, PEG 300monostearate, PEG 300 distearate, PEG 400 monostearate, PEG 600distearate, PEG 600 monostearate, PEG 200 distearate, PEG 1000monostearate, PEG 1000 distearate, PEG 1540 monostearate, PEG 1540distearate, PEG 4000 monostearate, PEG 4000 distearate, PEG 6000monostearate, PEG 6000 distearate, PEG 200 monooleate, PEG 200 dioleate,PEG 300 monooleate, PEG 300 dioleate, PEG 400 monooleate, PEG 600dioleate, PEG 600 monooleate, PEG 200 dioleate, PEG 1000 monooleate, PEG1000 dioleate, PEG 1540 monooleate, PEG 1540 dioleate, PEG 4000monooleate, PEG 4000 dioleate, PEG 6000 monooleate and PEG 6000dioleate.

In certain embodiments, the polymer used herein is PEG 400 distearate.In certain embodiments, PEG 400 distearate is present at a concentrationof about 0.1% by weight up to about 10% by weight of the total weight ofthe composition. In other embodiments, PEG 400 distearate is present ata concentration of about 0.1% by weight up to about 8% by weight of thetotal weight of the composition. In other embodiments, PEG 400distearate is present at a concentration of about 0.1% by weight up toabout 6% by weight of the total weight of the composition. In otherembodiments, PEG 400 distearate is present at a concentration of about0.1% by weight up to about 4% by weight of the total weight of thecomposition. In other embodiments, PEG 400 distearate is present at aconcentration of about 0.1% by weight up to about 2% by weight of thetotal weight of the composition. In other embodiments, PEG 400distearate is present at a concentration of about 2% by weight of thetotal weight of the composition. In other embodiments, PEG 400distearate is present at a concentration of about 1.8% by weight of thetotal weight of the composition. In other embodiments, PEG 400distearate is present at a concentration of about 1.5% by weight of thetotal weight of the composition. In other embodiments, PEG 400distearate is present at a concentration of about 1% by weight of thetotal weight of the composition. In other embodiments, PEG 400distearate is present at a concentration of about 0.1% by weight of thetotal weight of the composition.

e. Cosolvent

The compositions provided herein can also contain one or morecosolvents. Such cosolvents are non-toxic, pharmaceutically acceptablesubstances, typically liquids, which do not substantially negativelyaffect the solubility of the active agents at the concentrations used.The cosolvent can aid in dissolving the active agent or for themucoadhesive materials, or both. The cosolvent in certain embodiments,is a polyhydric alcohol or combination of polyhydric alcohols. Incertain embodiments, the cosolvent is ethylene glycol, dipropyleneglycol, propylene glycol, polyethylene glycol, glycerin, butyleneglycol, hexylene glycol, polyoxyethylene, polypropylene glycol,sorbitol, ethylene glycol, or a mixture thereof.

The amount of cosolvent in the compositions provided herein depends onthe solubility of the active agent and/or the mucoadhesive substance inthe oil or water phase. Typically, the cosolvent is present in an amountsufficient to achieve complete dissolution of the active agent. Incertain embodiments, the cosolvent is propylene glycol and is present ata concentration of about 1% by weight up to about 30% by weight of thetotal weight of the total composition. In other embodiments, propyleneglycol is present at a concentration of about 1% by weight up to about20% by weight of the total weight of the total composition. In otherembodiments, propylene glycol is present at a concentration of about 1%by weight up to about 15% by weight of the total weight of the totalcomposition. In other embodiments, propylene glycol is present at aconcentration of about 1% by weight up to about 10% by weight of thetotal weight of the total composition. In other embodiments, propyleneglycol is present at a concentration of about 15% by weight of the totalweight of the total composition. In other embodiments, propylene glycolis present at a concentration of about 13% by weight of the total weightof the total composition. In other embodiments, propylene glycol ispresent at a concentration of about 11% by weight of the total weight ofthe total composition. In other embodiments, propylene glycol is presentat a concentration of about 9.5% by weight of the total weight of thetotal composition. In other embodiments, propylene glycol is present ata concentration of about 7.5% by weight of the total weight of the totalcomposition. In other embodiments, propylene glycol is present at aconcentration of about 5% by weight of the total weight of the totalcomposition. In other embodiments, propylene glycol is present at aconcentration of about 3% by weight of the total weight of the totalcomposition. In other embodiments, propylene glycol is present at aconcentration of about 1% by weight of the total weight of the totalcomposition.

f. Other Additives

The compositions provided herein can further contain one or more otheradditives such as taste modifying agents, a buffering agent, a chelatingagent, a colorant, an osmotic modifier, a preservative, a sterilizer, asolubilizer, a tonicifier, a trace element, and a viscomodulator.

Taste modifying agents for use herein include, but are not limited toflavoring agents, sweetening agents and taste masking agents and areexemplified by: the essential oils or water soluble extracts of menthol,wintergreen, peppermint, sweet mint, spearmint, natural and artificialvanilla, cherry, chocolate, fudge, butterscotch, cinnamon, clove, lemon,orange, raspberry, rose, spice, violet, herbal, fruit, strawberry,grape, pineapple, peach, kiwi, papaya, mango, coconut, apple, coffee,plum, watermelon, nuts, durean, green tea, grapefruit, banana, butter,cream custard, camomile, sugar, dextrose, lactose, mannitol, sucrose,xylitol, maltitol, acesulfame potassium, talin, glycyrrhizin, sucralose,aspartame, saccharin, sodium saccharin, sodium cyclamate and honey. Incertain embodiments, the taste modifying agent is selected from naturaland artificial vanilla, cream custard, banana, fudge, butterscotch,coconut and chocolate.

Buffering agents include, but are not limited to acidulants andalkalizing agents exemplified by citric acid, fumaric acid, lactic acid,tartaric acid, malic acid, as well as sodium citrate, sodium bicarbonateand carbonate, sodium or potassium phosphate and magnesium oxide.

Coloring agents for use in the compositions include, but are not limitedto FD & C coloring agents, natural coloring agents, and natural juiceconcentrates, pigments such as titanium oxide, silicon dioxide and zincoxide.

Stabilizers as used in the compositions provided herein, include, butare not limited to anti-oxidants, chelating agents, and enzymeinhibitors as exemplified by ascorbic acid, vitamin E, butylatedhydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate,dilauryl thiodipropionate, thiodiproprionic acid, gum guaiac, citricacid, edetic acid and its salts and glutathione.

The compositions can contain preservatives which include, but are notlimited sodium benzoate, potassium sorbate, parabens and derivatives,such as methyl paraben, propyl paraben, sorbic acid and its salts,propionic acids and its salts, sulfur dioxide and sulfites, acetic acidand acetates, and nitrites and nitrates.

g. Exemplary Compositions

Provided herein are compositions containing one or more agentsformulated for mucosal delivery. The compositions provided are oil inwater or water in oil emulsions. In certain embodiments, the oil phasein the compositions contains oat oil. The oil phase further contains oneor more ingredients selected from the agent to be delivered, mediumchain triglycerides, propylene glycol, preservatives and surfactants.The water phase of the compositions contains water and one or moreingredients selected from preservatives, surfactants, agent to bedelivered and mucoadhesive proteins. In an exemplary embodiment, themucoadhesive protein is albumin, immunoglobulin or lactoferrin;preservatives are selected from one among potassium sorbate, sodiumbenzoate, methyl paraben, propyl paraben and benzyl alcohol; thesurfactants are phosphatidylcholine and polysorbate-80.

The compositions can contain oat oil from about 3% by weight up to about25% by weight, generally about 3%, 4%, 7%, 7.5%, 8%, 15% or 25% byweight of the composition. The amount of MCT in the composition can befrom about 10% by weight up to about 35% by weight, generally, 11%, 13%,17%. 30% or 31% by weight of the composition. An exemplary compositioncan contain propylene glycol from about 8% by weight up to about 12% byweight, typically, 1%, 8%, 9%, 10% or 11% by weight of the composition.The mucoadhesive proteins are present, for example, from about 1% byweight up to about 11% by weight, typically 9%, 9.5% or 10% by weight ofthe composition.

C. Methods of Manufacturing the Compositions

The compositions provided herein are stable emulsions of oil in water orwater in oil and are prepared by dissolving the components of thecomposition in the oil and/or water phases and mixing the two phasesunder constant temperature and pressure. They can be prepared by anysuitable method for making emulsions.

1. Equipment Used in Exemplary Procedures Provided Herein Include:

i) Tanks

Two tanks, one for the oil phase and the other for a water phase. Thesize of the tank can vary depending on the amount of oil and waterrequired to prepare the emulsion.

ii) Mixers

Mixers are used to blend, mix, emulsify and keep the materialcirculating in order to maintain temperature, viscosity, and otherparameters to ensure the product meets the desired consistency. Mixersused in the procedures herein are: shears, inline mixers/mixing, Ribbon,Plow/Paddle Blenders, Forberg Mixers, Conveyors, Bag Dumps & Compactors,V-Blenders, Blade Mixers, Double Cone Mixers, Continuous Mixers,Speedflow Mixers, Batch Mixers, Double Ribbon Blenders, Paddle andRibbon Mixers with Choppers, Plow Blenders/Turbulent Mixers, FluidizingForberg-Type Mixers, Air Mixers, Active Mixers, Passive Mixers, TopEntry Mixers, Side Entry Mixers, Static Mixers, Fixed Entry Mixers,Portable Mixers—both direct and gear drive, Sanitary Mixers, DrumMixers, Bulk Container (IBC) Mixers, Lab Stirrers, Variable SpeedMixers, dough mixer, vertical mixer, spiral mixer, twin arm mixer, forkmixer, double spiral mixer, all agitators, and any other mixerapplicable, agitator mixer, Banbury Mixer, Rubber Mixer, BlondheimMixer, Churn Mixer, Conical Mixer, Continuous Mixer, Disperser Mixer,Pan Mixer, Emulsifier Mixer, Hobart Mixer, Liquifier Mixer, LittlefordMixer, Meat Mixer, Plow Mixer, Mixmuller Mixer, Nauta Mixer, OakesMixer, Planetary Mixer, Pony Mixer, PUG Mixer, Ribbon Mixer, Ross Mixer,Rotary Mixer, Sigma Mixer, Single Arm Mixer, Tote Bin Mixer, TumbleMixer, Tumble Mixer, Vacuum Mixer, Turbolizer Mixer, Twin Shell Mixer,V-Type Mixer, Zig-Zag Mixer or side arm mixer.

iii) Heating Apparatus

Heating apparatus are used to heat the oil, water and emulsion phasesand for cleaning/sanitizing equipment before and after use. Exemplaryheating apparatus that can be used in the procedures provided hereinare: Electrical jacketed tanks/kettles, water jacketed tanks/kettles,submersible heaters, semi-submersible heaters, immersible heaters,over-the-side heaters, straight hairpin heater tubes, steel sheathheaters, circular shaped heater tubes, incoloy sheath heaters, stripheaters, finned strip heaters, enclosure heaters, cartridge heaters,bolt heaters, component tubular heaters, finned tubular heaters,explosion resistant heaters, preweld heaters, bushing heaters, flangedheaters, bottom outlet heaters, circulation heaters, low temperatureduct heaters and process heaters and other applicable heater apparatus.

Temperatures for heating solution and for cleaning/sanitizing range from65° F. to about 220° F. During the dissolving and mixing steps, thetemperature of the oil, water and emulsion phase is maintained at alevel where the components of the composition retain their activity, forexample the temperature is maintained such that the mucoadhesive proteindoes not denature during the process and the agent to be delivered doesnot degrade. A suitable temperature during the mixing step can bedetermined empirically for a particular combination of ingredients inthe composition. Typically, the temperature is maintained at about100-120° F., in some embodiments, at about 115° F. In certainembodiments, the temperature of the oil, water and emulsion phase duringthe process is maintained at about 120° F. In other embodiments, thetemperature of the oil, water and emulsion phase is maintained at about100° F. In other embodiments, the temperature is maintained at about60-70° F. In other embodiments, the temperature is maintained at about50° F.

The pressure for water jackets is maintained at a level selected so thatthe components of the composition do not degrade. In certainembodiments, the pressure is maintained at a range from 1 PSI to 120 PSI(pounds per square inch). In certain embodiments, the pressure is 50PSI. In other embodiments, the pressure is 30 PSI. In other embodiments,the pressure is 25 PSI. In other embodiments, the pressure is 10 PSI.

2. Exemplary Procedures for Preparing the Compositions

Exemplary procedures for preparing the compositions are described below:

a. Procedure A

Included among the compositions provided herein are oil in wateremulsions where the agent to be delivered is soluble in the water phaseor in the oil phase. Such compositions can be prepared by any suitablemethod known in the art, including the following procedure. Thecompositions are prepared at a temperature and pressure at which all theoil and water soluble components are soluble in the oil and waterphases, respectively and the mucoadhesive protein and the agent to bedelivered are not degraded in any way. For example, the temperature forheating the solution can be maintained at about 100°-150° F., in certainembodiments, 115° F., for all phases; and the pressure is at maintainedabout 20-30 pounds-per-square inch (PSI). In certain embodiments, whenusing this range and a water jacket, the pressure can be about 25 PSI.

i) Oil Phase

The oils used in the oil phase are weighed, added in a suitable vessel,such as a reactor tank and mixed to form a solution. The solution isheated and maintained at a temperature where all the oil solublecomponents can be dissolved in the oil phase while retaining theiractivity. A suitable temperature during the mixing step can bedetermined empirically for a particular combination of ingredients inthe composition. Typically, the temperature is maintained at about100-120° F., in some embodiments at about 115° F. A cosolvent, such aspropylene glycol, is weighed and mixed with the oil solution at a speedwhere complete dissolution of the ingredients is achieved withoutdenaturing or otherwise leading to degradation of the any activeingredients. Generally, mixing is carried out at about 10 rpm, 50 rpm,100 rpm, 150 rpm, 200 rpm, 250 rpm, 300 rpm or up to about 1000 rpm inoil phase. The oil preservatives, for example, methyl paraben and propylparaben are weighed and added to the oil phase and the mixture is mixedto dissolve the preservatives. A sterile solution of benzyl hydroxide orbenzyl benzoate is added and dissolved in the solution followed byaddition of emulsifiers, lipids, phospholipids and polymers. If theagent to be delivered is soluble in the oil phase, it is added and mixedto dissolve. The temperature and pressure are maintained throughout theprocedure to retain the activity of the agent to be delivered. Incertain embodiments, the reactor vessel is closed to prevent evaporationof any of the ingredients or maintained at other conditions thatminimize evaporation, such as contained in a beaker in small volume.When the combination of ingredients is such that evaporation is not aproblem, the reaction vessel does not necessarily have to be sealed.

ii) Water Phase

The required amount of water used in the water phase is weighed andadded in a suitable vessel, such as a reactor tank. The water phase isheated and maintained at a predetermined temperature such that themucoadhesive protein and the active agent, when soluble in the waterphase, retain their activities. For example, in the compositions thatcontain lactoferrin, the temperature is maintained at or below 100degrees F. or about 115° F., but not lower than 65-68 degrees F. inorder prevent lactoferrin from denaturing. The temperature and pressureare monitored and maintained throughout the procedure. Thepreservatives, for example, Na Benzoate and K Sorbate are weighed andadded to the water phase and the mixture is mixed to dissolve thepreservatives. A predetermined amount of lipids, phospholipids andpolymers to achieve a stable emulsion is added and dissolved. Thetemperature of the water phase is maintained at all times at a levelthat prevents denaturation of the mucoadhesive proteins. Themucoadhesive protein, required in an amount sufficient to achievequantitative delivery of the agent to be delivered, is added to thewater phase and mixed to dissolve. Where the agent to be delivered iswater soluble, it is added and mixed to dissolve. The mixing is carriedout at a speed where complete dissolution of the ingredients is achievedwithout denaturing or otherwise leading to degradation of the any activeingredients. Generally, mixing is carried out at about 10 rpm, 50 rpm,100 rpm, 150 rpm, 200 rpm, 250 rpm, 300 rpm or up to about 1000 rpm inwater phase. In certain embodiments, the reactor vessel, such as reactortank, is closed to prevent evaporation of any of the ingredients ormaintained at other conditions that minimize evaporation, such ascontained in a beaker in small volume. When the combination ofingredients is such that evaporation is not a problem, the reactionvessel does not necessarily have to be sealed.

iii) Formation of Emulsion

The oil phase is added to the water phase. This can be achieved, forexample, by pumping, manually adding or any other means of transferringfrom the oil tank to the water tank. As the oil phase is being added tothe water phase, the mixture is mixed at a speed sufficient to createthe emulsion without denaturing or otherwise leading to degradation ofthe any active ingredients. The mixing can be effected at about 100 rpm,300 rpm, 500 rpm, 700 rpm, 1000 rpm, 10,000 rpm, 20,000 rpm, 30,000 rpm,40,000 rpm, 50,000 rpm, 60,000 rpm or up to about 100,000 rpm. Themixing step can involve shearing or just light mixing to create theemulsion. In certain embodiments, mixing is achieved by shearing. Incertain embodiments, the pH of the emulsion is a function of themucoadhesive protein used. The emulsion is maintained at neutral orbasic pH throughout these steps.

b. Procedure B

Included among the compositions provided herein are water-in-oilemulsions, where the agent for delivery is soluble in the oil phase.They can be prepared by any suitable method, including the followingprocedure and any modifications thereof. In all phases the temperatureand pressure of the solution are maintained at a level sufficient todissolve all the ingredients while retaining the activity ofmucoadhesive protein and the agent to be delivered. The temperaturegenerally is maintained at about 90° F. to 110° F., typically at about100° F. or 115° F. A suitable temperature during the mixing step can bedetermined empirically for a particular combination of ingredients inthe composition. Typically, the temperature is maintained at about100-120° F., in some embodiments, at about 115° F. Pressure is adjustedto achieve the dissolution of the components while maintaining theactivity of the mucoadhesive protein and the agent to be delivered. Forthe temperature range used in the procedures provided herein, thepressure (in pounds-per-square inch PSI) is in the range of about 20 toabout 30 PSI, typically the pressure in the water jacket for heating themixture is maintained at about 25 PSI. Generally the water phase isadded to the oil phase to produce a composition for mucosal delivery.

i) Oil Phase

The oils used in the oil phase are weighed and mixed. The solution isheated up to and maintained at a temperature where all the oil solublecomponents can be dissolved in the oil phase while retaining theiractivity, typical temperature is 100° F. and the temperature ismaintained throughout the procedure. In some embodiments, suitabletemperature during the mixing step can be determined empirically for aparticular combination of ingredients in the composition. Typically, thetemperature is maintained at about 115° F. A cosolvent, such aspropylene glycol is weighed and dissolved at a predetermined RPM wherebycomplete dissolution of ingredients is achieved without denaturing orotherwise leading to degradation of the any active ingredients. Requiredamount of oil preservatives, such as methyl paraben and propyl parabenare added to oil phase, followed by sterile solution of benzyl hydroxideor benzyl benzoate. Emulsifiers are added and mixed to the oil phase,followed by addition of required amounts of lipids, phospholipids andpolymers. Any oil soluble active agent is then weighed and added to theoil phase. In certain embodiments, the reactor vessel is closed toprevent evaporation of any of the ingredients or maintained at otherconditions that minimize evaporation, such as contained in a beaker insmall volume. When the combination of ingredients is such thatevaporation is not a problem, the reaction vessel does not necessarilyhave to be sealed.

ii) Water Phase

The required amount of water used in the water phase is weighed andadded in a reactor tank. Water is heated and maintained at a temperaturesuitable for dissolution of the mucoadhesive protein and to prevent anydegradation of the agent to be delivered. A cosolvent, such as propyleneglycol is weighed and dissolved. Preservatives, for example, Na Benzoateand K Sorbate are weighed and added to the water phase and the mixtureis mixed to dissolve the preservatives. Required amount of lipids,phospholipids and polymers to achieve stable emulsion are added anddissolved. For the compositions containing mucoadhesive proteins, suchas lactoferrin, temperature is maintained at or below 100 degrees F., incertain embodiments, 115° F., but not lower than room temperature inorder prevent the protein from denaturing. Temperature and pressure aremaintained throughout the procedure. The mucoadhesive protein, requiredin an amount sufficient to achieve quantitative delivery of the agent tobe delivered, is added to the water phase and mixed to dissolve. Anagent to be delivered, if soluble in the water phase, is added and mixedto dissolve. In certain embodiments, the reactor vessel, such as reactortank, is closed to prevent evaporation of any of the ingredients ormaintained at other conditions that minimize evaporation, such ascontained in a beaker in small volume. When the combination ofingredients is such that evaporation is not a problem, the reactionvessel does not necessarily have to be sealed.

iii) Formation of Emulsion

The water phase is added to the oil phase. This can be achieved, forexample, by pumping, manually adding or any other means of transferringfrom the oil tank to the water tank. As the oil phase is being added tothe water phase, the mixture is mixed at a speed sufficient to createthe emulsion without denaturing or otherwise leading to degradation ofthe any active ingredients. The mixing can be effected at about 100 rpm,300 rpm, 500 rpm, 700 rpm, 1000 rpm, 10,000 rpm, 20,000 rpm, 30,000′rpm, 40,000 rpm, 50,000 rpm, 60,000 rpm or up to about 100,000 rpm. Incertain embodiments, mixing is achieved by shearing. The emulsion ismaintained at a temperature lower than the denaturing temperature ofproteins, typically at about 100° F. or about 115° F. The emulsion ismaintained at neutral or basic pH during these steps.

c. Procedure C

This procedure can be used for either oil in water or water in oilemulsion where the agent to be delivered is soluble in the water phaseor in the oil phase. Such compositions can be prepared by any suitablemethod known in the art, including the following procedure. Thecompositions are prepared at a temperature and pressure at which all theoil and water soluble components are soluble in the oil and waterphases, respectively and the mucoadhesive protein and the agent to bedelivered are not degraded in any way. For example, the temperature forheating the solution can be maintained at about 100°-150° F. for allphases; and the pressure is at maintained about 20-30 pounds-per-squareinch (PSI). For example, when using temperature in this range and awater jacket, the pressure can be about 25 PSI.

i) Oil Phase

Required amounts of all the oils used in this oil phase are weighed andmixed. The solution is heated and maintained at a temperature where allthe oil soluble components can be dissolved in the oil phase whileretaining their activity. In certain embodiments, the temperature ismaintained at about 100° F.-150° F., typically at 100° F., or about 115°F. for all phases. A cosolvent, such as propylene glycol is weighed anddissolved at a predetermined RPM whereby complete dissolution ofingredients is achieved without denaturing or otherwise leading todegradation of the any active ingredients. Required amount of oilpreservatives, such as methyl paraben and propyl paraben are added tooil phase, followed by sterile solution of benzyl hydroxide or benzylbenzoate. Emulsifiers are added and mixed in the oil phase, followed byaddition of required amounts of lipids, phospholipids and polymers toachieve a stable emulsion. If the agent to be delivered is soluble inthe oil phase, it is added and mixed to dissolve. The temperature andpressure are maintained throughout the procedure to retain the activityof the agent to be delivered. In certain embodiments, the reactorvessel, such as reactor tank, is closed to prevent evaporation of any ofthe ingredients or maintained at other conditions that minimizeevaporation, such as contained in a beaker in small volume. When thecombination of ingredients is such that evaporation is not a problem,the reaction vessel does not necessarily have to be sealed.

ii) Water Phase

The required amount of water used in the water phase is weighed andadded in a reactor tank. The water phase is heated and maintained at apredetermined temperature such that the mucoadhesive protein and theactive agent, when soluble in water phase, retain their activities. Forexample, in the compositions that contain lactoferrin, the temperatureis maintained at or below 100 degrees F., or about 115° F. but not lowerthan 65-68 degrees F. in order prevent lactoferrin from denaturing. Thetemperature and pressure are monitored and maintained throughout theprocedure. A cosolvent, such as propylene glycol is weighed anddissolved at a predetermined RPM whereby complete dissolution of theingredients is achieved without denaturing or otherwise leading todegradation of the any active ingredients. Preservatives, for example,Na Benzoate and K Sorbate are weighed and added to the water phase andthe mixture is mixed to dissolve the preservatives. Required amount oflipids, phospholipids and polymers to achieve stable emulsion are addedand dissolved. Temperature and pressure are maintained throughout theprocedure. The mucoadhesive protein, required in an amount sufficient toachieve quantitative delivery of the agent to be delivered, is added tothe water phase and mixed to dissolve. Where the agent to be deliveredis water soluble, it is added and mixed to dissolve. In certainembodiments, the reactor vessel, reactor tank is closed to preventevaporation of any of the ingredients or maintained at other conditionsthat minimize evaporation, such as contained in a beaker in smallvolume. When the combination of ingredients is such that evaporation isnot a problem, the reaction vessel does not necessarily have to besealed.

iii) Formation of Emulsion

The water phase is added to the oil phase or oil phase can be added towater phase. This can be achieved, for example, by pumping, manuallyadding or any other means of transferring from the oil tank to the watertank. As the two phases are being added, the mixture is mixed at a speedsufficient to create the emulsion without denaturing or otherwiseleading to degradation of the any active ingredients. The mixing can beeffected at about 100 rpm, 300 rpm, 500 rpm, 700 rpm, 1000 rpm, 10,000rpm, 20,000 rpm, 30,000 rpm, 40,000 rpm, 50,000 rpm, 60,000 rpm or up toabout 100,000 rpm. The mixing step can involve shearing or just lightmixing to create the emulsion. In certain embodiments, mixing isachieved by shearing. The emulsion is maintained at a temperature lowerthan the denaturing temperature of proteins, typically at about 100° F.or about 115° F. The emulsion is maintained at neutral or basic pH (pH8-9) throughout these steps.

It is noted that various parameters described in the general proceduresdescribed above for the preparation of the water in oil and oil in wateremulsions represent exemplary embodiments and are not intended to limitthe scope of the subject matter provided herein.

D. Formulations

The compositions provided herein contain one or more agents foradministration to a subject via the mucosa. The agents can be anythingto be administered and in any amount. Typically the compositions containtherapeutically effective amounts of one or more biologically activeagents that alter a biological function, such as a body function at thecellular, tissue or organ level and/or alters cosmetic appearance of asubject. In certain embodiments, the compositions provided herein areintended for delivery of biologically active agents through oral ornasal mucosa, thereby allowing for the avoidance of the gastrointestinaltract and first pass liver metabolism and consequently allowing thebiologically active agent to directly enter into circulation.

The compositions provided herein are useful in altering a biologicalfunction, such as a body function at the cellular, tissue or organ leveland/or altering cosmetic appearance of a subject. In certainembodiments, the compositions provided herein are useful in theprevention, treatment, or amelioration of one or more of the symptoms ofdiseases or disorders that can be treated by any agent that can bedelivered to a mucosal surface via the compositions provided herein. Thediseases or disorders treatable by the compositions provided include,but are not limited to neural disorders, respiratory disorders, immunesystem disorders, muscular disorders, reproductive disorders,gastrointestinal disorders, pulmonary disorders, digestive disorders,metabolic disorders, cardiovascular disorders, renal disorders,proliferative disorders, cancerous diseases and inflammation.

The compositions provided herein contain one or more agent to bedelivered or pharmaceutically acceptable derivatives thereof. Thecompositions can be formulated into stable emulsions for mucosaldelivery. In certain embodiments, the compositions have been found to bestable for up to 6 months.

The compositions are formulated as emulsions for administration to theoral or nasal mucosal membranes. Typically the compositions describedabove are formulated using techniques and procedures well known in theart (see, e.g., Ansel (1985) Introduction to Pharmaceutical DosageForms, Fourth Edition, p. 126)), including the procedures describedabove.

Typically, in the compositions provided herein, one or more agents to bedelivered or pharmaceutically acceptable derivatives thereof is (are)present in the concentration that is effective for delivery of anamount, upon administration, that alters a biological function, such asa body function at the cellular, tissue or organ level and/or alterscosmetic appearance of a subject. Such alteration of a biologicalfunction or cosmetic appearance includes, but is not limited totreatment of diseases or disorders including, but are not limited to,neural disorders, respiratory disorders, immune system disorders,muscular disorders, reproductive disorders, gastrointestinal disorders,pulmonary disorders, digestive disorders, metabolic disorders,cardiovascular disorders, renal disorders, proliferative disorders,cancerous diseases and inflammation.

The compositions typically contain an agent to be delivered in an amountsufficient to exert a therapeutically useful effect in the absence ofundesirable side effects on the subject. It is understood that thenumber and degree of side effects depends upon the condition for whichthe compositions are administered. For example, certain toxic andundesirable side effects are tolerated when treating life-threateningillnesses, such as tumors, that would not be tolerated when treatingdisorders of lesser consequence.

The concentration of the agent to be delivered in the composition willdepend on absorption, inactivation and excretion rates thereof, thedosage schedule, and amount administered as well as other factors knownto those of skill in the art. Typically a therapeutically effectivedosage should produce a serum concentration of active ingredient fromabout 0.1 ng/ml to about 50-100 μg/ml. The compositions typically shouldprovide a dosage of from about 0.01 mg to about 100-2000 mg of the agentto be delivered, depending upon the agent selected and adjusted for bodysurface area and/or weight. Typically, a daily dosage of about between0.05 mg/kg and 0.5 mg/kg, in certain embodiments 10 mg/kg should besufficient. The dosage is a function of the agent delivered. In certainembodiments, single dosages per administration contain 1-2 millilitersof 1, 10, 100, 200, 250, 500, 650, 1000, 1500, or 2000-2500 mgs of totalmaterial delivered and is a function of the agent delivered. In certainembodiments, 1, 2, 3, 4, 5 or more servings of the composition can beadministered per day depending upon the agent delivered and diseasetreated. It is understood that the amount to administer is a function ofthe agent to be delivered, the alteration of a biological function orcosmetic appearance desired, and possibly the side effects that will betolerated. Dosages can be empirically determined using recognized modelsfor each effect desired.

Typically, the compositions are provided for administration to humansand animals in unit or multiple dosage forms as oil-water emulsionscontaining suitable quantities of one or more agents to be delivered orpharmaceutically acceptable derivative thereof. The unit-dose forms asused herein refers to physically discrete units suitable for human andanimal subjects and packaged individually as is known in the art. Eachunit-dose contains a predetermined quantity of the agent to be deliveredsufficient to produce the desired effect, in association with therequired additives in the composition. Unit-dose forms can beadministered in fractions or multiples thereof.

Examples of unit dosage include capsules filled with liquidcompositions. A multiple-dose form is a plurality of identicalunit-dosage forms packaged in a single container to be administered insegregated unit-dose form. Examples of multiple-dose forms include vialsand bottles.

E. Methods of Use of the Compositions

Provided herein are methods of mucosal delivery of agents to subjects.The methods for mucosal delivery of an agent provided herein includeproviding a composition for mucosal delivery and contacting thecomposition with a mucosal surface of a subject, whereby the agent isdelivered into the circulatory system of the subject. Contacting amucosal surface, such as the oral, nasal or other mucosal surface, of asubject with a composition provided herein permits delivery of thecomposition and hence of any selected agent that can be formulated as anemulsion. Contacting can be effected by any suitable method. Forexample, methods provided herein include the steps of providing apharmaceutical composition as described herein, including an agent fordelivery and administering the composition to the mucosa of the subject,generally either by oral, intranasal inhalation or other method wherebythe composition contacts mucosa in the subject.

In the methods provided herein, the compositions can contact, adhereand/or penetrate into the mucosal lining from about 1 minute up to about24 hours or more, typically, about 1, 2, 3, 5, 10, 15, 20, 30, 60, or120 minutes. In some embodiments, in the methods provided herein, thecompositions can contact, adhere and/or penetrate into the mucosallining for about 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 or up to 24hours.

The compositions provided herein can be administered by methods known tothose of skill in the art, including, but not limited to delivering thecomposition in oral cavity or nasal cavity. The composition can besprayed into the oral cavity or nasal cavity, administered as softcapsule filled with the liquid composition or contacted to the mucosalsurface in the oral and nasal cavity by any other means known in theart. When delivering with a soft capsule, the capsule can then be chewedby the subject to release the composition into the oral cavity. Theintranasal composition is applied to the nasal mucosa via topicalapplication (spray and/or drops) of a safe and effective amount of thecomposition. The frequency of administration of the composition mayvary, depending upon personal or medical needs, but generally rangesfrom about once per day to about four times daily.

The compositions are designed for delivery to a mucosal membrane wherebythe agent to be delivered gets absorbed into the mucosa and directlyenters into circulation. The amount of agent that is absorbed throughthe mucosal lining can be assessed by methods known in the art anddescribed herein. For example, the amount of agent absorbed can beassessed by measuring the amount of agent administered to the subjectand comparing it to the amount thereof found in a blood sample. Theblood sample can be obtained at different time intervals. The intervalof time can be empirically determined based on such factors as the agentto be delivered and the mode of administration. The amount of agent tobe delivered per dosage depends on the amount of agent absorbed throughthe mucosal lining and other factors such as age and physical conditionof the subject.

In certain embodiments, the methods are used for delivery of minerals,vitamins, pharmaceutical drugs, nutritional supplements, hormones, orthe like, which when introduced into the body cause a desired biologicalresponse, such as altering body function at the cellular, tissue ororgan level or altering cosmetic appearance. In certain embodiments, theagent delivered is a drug or other pharmaceutical ingredient,particularly one that has a significant loss of activity in the lumen ofthe gastrointestinal tract or in the tissues of the gastrointestinaltract during the absorption process or upon passage through the liverafter absorption in the intestinal tract. In certain embodiments, themethods provided herein are useful for delivery of one or more activeagents selected from anticonvulsants, analgesics, antiparkinsons,anti-inflammatories, calcium antagonists, anesthetics, antimicrobials,antimalarials, antiparasitics, antihypertensives, antihistamines,antipyretics, alpha-adrenergic agonists, alpha-blockers, biocides,bactericides, bronchial dilators, beta-adrenergic blocking drugs,contraceptives, cardiovascular drugs, calcium channel inhibitors,depressants, diagnostics, diuretics, electrolytes, enzymes, hypnotics,hormones, hypoglycemics, hyperglycemics, muscle contractants, musclerelaxants, neoplastics, glycoproteins, nucleoproteins, lipoproteins,ophthalmics, psychic energizers, sedatives, steroids, sympathomimetics,parasympathomimetics, tranquilizers, urinary tract drugs, vaccines,vaginal drugs, vitamins, minerals, nonsteroidal anti-inflammatory drugs,angiotensin converting enzymes, polynucleotides, polypeptides,polysaccharides, and nutritional supplements including herbalsupplements.

Hence, provided herein are methods for treatment of diseases ordisorders that can be treated by mucosal administration of activeagents, such diseases and disorders include, but are not limited toneural disorders, respiratory disorders, immune system disorders,muscular disorders, reproductive disorders, gastrointestinal disorders,pulmonary disorders, digestive disorders, metabolic disorders,cardiovascular disorders, renal disorders, proliferative disorders,cancerous diseases and inflammation.

The immune system disorders that can be treated by the compositionsprovided herein include, but are not limited to systemic lupuserythematosus, rheumatoid arthritis, ankylosing spondylitis, multiplesclerosis, insulin resistant diabetes mellitus, autoimmune thyroiditis,Hashimoto's thyroiditis, autoimmune hemolytic anemia, hemolytic anemia,thrombocytopenia, autoimmune thrombocytopenia purpura, autoimmuneneonatal thrombocytopenia, idiopathic thrombocytopenia purpura,autoimmunocytopenia, Goodpasture's syndrome, myasthenia gravis, Grave'sdisease (hyperthyroidism), type II collagen-induced arthritis,antiphospholipid syndrome, dermatitis, allergic encephalomyelitis,myocarditis, relapsing polychondritis, rheumatic heart disease,neuritis, uveitis ophthalmia, polyendocrinopathies, Reiter's Disease,Stiff-Man Syndrome, autoimmune pulmonary inflammation, autism,Guillain-Barre Syndrome, insulin dependent diabetes mellitus, autoimmuneinflammatory eye disorders, scleroderma with anti-collagen antibodies(often characterized, e.g., by nucleolar and other nuclear antibodies),mixed connective tissue disease (often characterized, e.g., byantibodies to extractable nuclear antigens (e.g., ribonucleoprotein)),polymyositis (often characterized, e.g., by nonhistone ANA), perniciousanemia (often characterized, e.g., by antiparietal cell, microsomes, andintrinsic factor antibodies), idiopathic Addison's disease (oftencharacterized, e.g., by humoral and cell-mediated adrenal cytotoxicity,infertility (often characterized, e.g., by antispermatozoal antibodies),glomerulonephritis (often characterized, e.g., by glomerular basementmembrane antibodies or -immune complexes), bullous pemphigoid (oftencharacterized, e.g., by IgG and complement in basement membrane),Sjogren's syndrome (often characterized, e.g., by multiple tissueantibodies, and/or a specific nonhistone ANA (SS-B)), diabetes mellitus(often characterized, e.g., by cell-mediated and humoral islet cellantibodies), and adrenergic drug resistance (including adrenergic drugresistance with asthma or cystic fibrosis) (often characterized, e.g.,by beta-adrenergic receptor antibodies), chronic active hepatitis (oftencharacterized, e.g., by smooth muscle antibodies), primary biliarycirrhosis (often characterized, e.g., by mitochondria antibodies), otherendocrine gland failure (often characterized, e.g., by specific tissueantibodies in some cases), vitiligo (often characterized, e.g., bymelanocyte antibodies), vasculitis (often characterized, e.g., by Ig andcomplement in vessel walls and/or low serum complement), post-M-1 (oftencharacterized, e.g., by myocardial antibodies), cardiotomy syndrome(often characterized, e.g., by myocardial antibodies), urticaria (oftencharacterized, e.g., by IgG and IgM antibodies to IgE), atopicdermatitis (often characterized, e.g., by IgG and IgM antibodies toIgE), asthma (often characterized, e.g., by IgG and IgM antibodies toIgE), and many other inflammatory, granulomatous, degenerative, andatrophic disorders.

In certain embodiments, the compositions are used in the methods totreat allergy related conditions, including, but not limited to allergicreactions include, but are not limited to, asthma, rhinitis, and eczema.

In certain embodiments, the compositions are used in the methods totreat inflammatory conditions including, but are not limited to, forexample inflammation associated with infection (e.g., septic shock,sepsis, or systemic inflammatory response syndrome),ischemia-reperfusion injury, endotoxin lethality, complement-mediatedhyperacute rejection, nephritis, cytokine or chemokine induced lunginjury, inflammatory bowel disease, Crohn's disease, overproduction ofcytokines (e.g., TNF or IL-1), respiratory disorders (e.g., asthma andallergy); gastrointestinal disorders (e.g., inflammatory bowel disease);cancers (e.g., gastric, ovarian, lung, bladder, liver, and breast); CNSdisorders (e.g., multiple sclerosis; ischemic brain injury and/orstroke, traumatic brain injury, neurodegenerative disorders (e.g.,Parkinson's disease and Alzheimer's disease); AIDS-related dementia; andprion disease); cardiovascular disorders (e.g., atherosclerosis,myocarditis, cardiovascular disease, and cardiopulmonary bypasscomplications); as well as many additional diseases, conditions, anddisorders that are characterized by inflammation (e.g., hepatitis,rheumatoid arthritis, gout, trauma, pancreatitis, sarcoidosis,dermatitis; renal ischemia-reperfusion injury, Grave's disease, systemiclupus erythematosus, diabetes mellitus; and allogenic transplantrejection).

In certain embodiments, the methods provided herein are useful fortreatment of cancers or neoplasms that include, but are not limited to,myelogenous leukemia, Hodgkin's disease, non-Hodgkin's lymphoma,lymphocyte leukemia, plasmacytomas, multiple myeloma, Burkitt'slymphoma, EBV-transformed diseases, hyperproliferative disordersLymphoblastic Leukemia, Myeloid Leukemia, Adrenocortical Carcinoma,Hepatocellular Cancer, Liver Cancer, Soft Tissue Sarcoma, Anal Cancer,Astrocytoma, Bile Duct Cancer, Bladder Cancer, Bone Cancer, Brain StemGlioma, Brain Tumors, Breast Cancer, Cancer of the Renal Pelvis andUreter, Cerebellar Astrocytoma, Cerebral Astrocytoma, Cervical Cancer,Colon Cancer, Endocrine Pancreas Islet Cell Carcinoma, EndometrialCancer, Ependymoma, Epithelial Cancer, Esophageal Cancer, Ewing'sSarcoma and Related Tumors, Exocrine Pancreatic Cancer, ExtracranialGerm Cell Tumor, Extragonadal Germ Cell Tumor, Extrahepatic Bile DuctCancer, Eye Cancer, Breast Cancer, Gaucher's Disease, GallbladderCancer, Gastric Cancer, Gastrointestinal Carcinoid Tumor, Germ CellTumors, Gestational Trophoblastic Tumor, Hairy Cell Leukemia, Head andNeck Cancer, Hepatocellular Cancer, Hypopharyngeal Cancer, IntestinalCancers, Intraocular Melanoma, Islet Cell Carcinoma, Islet CellPancreatic Cancer, Kaposi's Sarcoma, Kidney Cancer, Laryngeal Cancer,Lip and Oral Cavity Cancer, Liver Cancer, Lung Cancer,Lymphoproliferative Disorders, Macroglobulinemia, Melanoma, Nasal Cavityand Paranasal Sinus Cancer, Nasopharyngeal Cancer, and any otherhyperproliferative disease.

In certain embodiments, the methods provided herein are useful fortreatment of heart diseases, such as arrhythmias, carcinoid heartdisease, high cardiac output, low cardiac output, cardiac tamponade,endocarditis (including bacterial), heart aneurysm, cardiac arrest,congestive heart failure, congestive cardiomyopathy, paroxysmal dyspnea,cardiac edema, heart hypertrophy, congestive cardiomyopathy, leftventricular hypertrophy, right ventricular hypertrophy, post-infarctionheart rupture, ventricular septal rupture, heart valve diseases,myocardial diseases, myocardial ischemia, pericardial effusion,pericarditis (including constrictive and tuberculous),pneumopericardium, postpericardiotomy syndrome, pulmonary heart disease,rheumatic heart disease, ventricular dysfunction, hyperemia,cardiovascular pregnancy complications, Scimitar Syndrome;cardiovascular syphilis, and cardiovascular tuberculosis.

The methods provided in certain embodiment, are used for treatment ofdiseases and disorders of the respiratory system including, but are notlimited to, nasal vestibulitis, nonallergic rhinitis (e.g., acuterhinitis, chronic rhinitis, atrophic rhinitis, vasomotor rhinitis),nasal polyps, and sinusitis, juvenile angiofibromas, cancer of the noseand juvenile papillomas, vocal cord polyps, nodules (singer's nodules),contact ulcers, vocal cord paralysis, laryngoceles, pharyngitis (e.g.,viral and bacterial), tonsillitis, tonsillar cellulitis, parapharyngeal,abscess, laryngitis, laryngoceles, allergic disorders (eosinophilicpneumonia, hypersensitivity pneumonitis (e.g., extrinsic allergicalveolitis, allergic interstitial pneumonitis, organic dustpneumoconiosis, allergic bronchopulmonary aspergillosis, asthma,Wegener's granulomatosis (granulomatous vasculitis), Goodpasture'ssyndrome)), pneumonia (e.g., bacterial pneumonia (e.g., Streptococcuspneumoniae (pneumoncoccal pneumonia), Staphylococcus aureus(staphylococcal pneumonia), Gram-negative bacterial pneumonia (causedby, e.g., Klebsiella and Pseudomonas spp.), Mycoplasma pneumoniaepneumonia, Hemophilus influenzae pneumonia, Legionella pneumophila(Legionnaires' disease), and Chlamydia psittaci (Psittacosis)), andviral pneumonia (e.g., influenza, chickenpox (varicella), obstructiveairway diseases (e.g., asthma, chronic obstructive pulmonary disease(COPD), emphysema, chronic or acute bronchitis), occupational lungdiseases (e.g., silicosis, black lung (coal workers' pneumoconiosis),asbestosis, berylliosis, occupational asthmas, byssinosis, and benignpneumoconioses), Infiltrative Lung Disease (e.g., pulmonary fibrosis(e.g., fibrosing alveolitis, usual interstitial pneumonia), idiopathicpulmonary fibrosis, desquamative interstitial pneumonia, lymphoidinterstitial pneumonia, histiocytosis X (e.g., Letterer-Siwe disease,Hand-Schuller-Christian disease, eosinophilic granuloma), idiopathicpulmonary hemosiderosis, sarcoidosis and pulmonary alveolarproteinosis), Acute respiratory distress syndrome (also called, e.g.,adult respiratory distress syndrome), edema, pulmonary embolism,bronchitis (e.g., viral, bacterial), bronchiectasis, atelectasis, lungabscess (caused by, e.g., Staphylococcus aureus or Legionellapneumophila), and cystic fibrosis. In certain embodiments, the methodsare for treatment of autoimmune disorders, such as systemic lupuserythematosus, rheumatoid arthritis, ankylosing spondylitis, multiplesclerosis, autoimmune thyroiditis, Hashimoto's thyroiditis, autoimmunehemolytic anemia, hemolytic anemia, thrombocytopenia, autoimmunethrombocytopenia purpura, autoimmune neonatal thrombocytopenia,idiopathic thrombocytopenia purpura, purpura (e.g., Henoch-Schönleinpurpura), autoimmunocytopenia, Goodpasture's syndrome, myastheniagravis, Grave's disease (hyperthyroidism), and diabetes mellitus. Incertain embodiments, the methods are for treatment of diabetes.

In certain embodiments, the methods are for mucosal delivery of insulinto a subject in need thereof. In certain embodiments, the methods arefor delivery of dietary supplements, including but not limited tovitamins, minerals, hormones and antioxidants. In certain embodiments,the methods provided herein are for delivery of vitamins. In otherembodiments, the methods provided herein are for delivery of minerals.In other embodiments, the methods provided herein are for delivery ofcalcium. In other embodiments, the methods provided herein are fordelivery of COQ10. In other embodiments, the methods provided herein arefor delivery of testosterone.

F. Articles of Manufacture

The compositions provided herein can be packaged as articles ofmanufacture containing packaging material, a composition providedherein, and a label that indicates that the composition is for mucosaldelivery. In instances where the active agent is useful for altering abody function or altering cosmetic appearance of the subject, thecompositions can be packaged as articles of manufacture containingpackaging material, a composition provided herein suitable for mucosaladministration, and a label that indicates that the composition is usedfor altering a body function or altering cosmetic appearance of thesubject. In certain embodiments, the compositions can be packaged asarticles of manufacture containing packaging material, a compositionprovided herein suitable for mucosal administration, and a label thatindicates that the composition is used for delivery of dietarysupplements. In certain embodiments, the compositions can be packaged asarticles of manufacture containing packaging material, a compositionprovided herein suitable for mucosal administration, and a label thatindicates that the composition is used for delivering a therapeuticagent to a subject in need thereof.

The articles of manufacture provided herein contain packaging materials.Packaging materials for use in packaging pharmaceutical products arewell known to those of skill in the art. See, e.g., U.S. Pat. Nos.5,323,907, 5,052,558 and 5,033,252. Examples of pharmaceutical packagingmaterials include, but are not limited to, blister packs, bottles,tubes, inhalers, pumps, bags, vials, containers, bottles, and anypackaging material suitable for a selected formulation and intended modeof administration and treatment.

The following examples are exemplary only and are not intended to limitthe scope of the subject matter claimed herein.

EXAMPLE 1

Preparation of Calcium Formulation

Appropriate quantities of the raw materials were weighed for the 1.1 Kgbatch as shown below:

Ingredient (Oil) mg/serving %/serving mg/batch MCT (Neobee M-5) (in oil)1368.7 17.10875 171087.5 Oat Oil (in oil) 2046 25.575 255750 Water2088.3 26.10375 261037.5 Propylene Glycol (In Oil Phase) 830 10.375103750 K-Sorbate (in oil) 6 0.075 750 Na-Benzoate (in oil) 6 0.075 750Saladizer ® (In Water phase) 8 0.1 1000 Polymer (PEG 400 DS) (in oil)170 2.125 21250 Methyl Paraben (in oil) 3 0.0375 375 Propyl Paraben (inoil) 3 0.0375 375 Lecithin (in oil) 59 0.7375 7375 Polysorbate 80 (Inwater Phase) 300 3.75 37500 Calcium Citrate, 17% Ca (168 mg 820 10.25102500 of elemental Ca) Benzyl OH 35 0.4375 4375 Lactoferrin 94% (inwater) 50 0.625 6250 Luo Han Gao 80% 24 0.3 3000 Sucralose 59 0.73757375 Butterscotch (BU-166) 21 0.2625 2625 Coconut (CC-116) 24 0.3 3000Nat & Art. Vanilla (L-6729) 22 0.275 2750 Fudge (CT-151) 20 0.25 2500Chocolate (CT-147) 37 0.4625 4625 Totals 8000.000 100.0000 1100000

Water phase was prepared by weighing appropriate quantities of water,preservatives, polysorbate 80, lactoferrin, calcium, and Saladizer® gumblend, mixing the ingredients to dissolve all the components at 120° F.

Oil phase was prepared by weighing the appropriate amounts of oat oil,MCT, propylene glycol, methyl & propyl parabens, benzyl OH, PEG, andlecithin, heating the mixture to 120° F. and mixing until all theingredients dissolve.

Emulsion was prepared by heating the water and oil phases to 160° F.,and adding water phase to oil phase slowly while mixing. The emulsionwas cooled to 95° F., followed by addition of flavors/sweeteners andadditional water if needed to make up the batch of 1.1 Kg.

EXAMPLE 2

Preparation of Libido Formulation

Appropriate quantities of the raw materials were weighed for the 0.55 Kgbatch as shown below:

Ingredient (Oil) mg/serving %/serving mg/batch MCT (Neobee M-5) (Oil 30830.8 154000 Phase) Oat Oil (Oil Phase) 150.2 15.02 75100 Water 231 23.1115500 Propylene Glycol (In Oil 80 8 40000 Phase) K-Sorbate (Preserves)(Water 2 0.2 1000 phase) Na-Benzoate (Preserves) 2 0.2 1000 (Waterphase) Polymer (PEG 400 DS) (Oil 20 2 10000 Phase) Methyl Paraben (OilPreserves) 1 0.1 500 Propyl Paraben (Oil Preserves) 1 0.1 500 Lecithin(Ultralec-P, 15 1.5 7500 Phospholipids) (Oil Phase) Polysorbate-80(Lipids) (In 35 3.5 17500 water Phase, after filter after Salidizer)Benzyl OH (Sterilizer, protein 5 0.5 2500 preserver) (Oil Phase)Testosterone (in Oil, in 75 7.5 37500 liposome) Vinpocetine (in Oil, in6 0.6 3000 liposome) (Lactoferrin 94% minimum) 52 5.2 26000 (Waterphase) Sucralose (At the end) 12 1.2 6000 Nat. Banana (BA-133) (At theend) 3.4 0.34 1700 Nat & Art. Vanilla (VA-158) 1.4 0.14 700 (At the end)Totals 1000.000 100.0000 550000

Water phase was prepared by weighing appropriate quantities of water,preservatives, polysorbate 80, and lactoferrin mixing the ingredients todissolve all the components at 130-140° F.

Oil phase was prepared by weighing the appropriate amounts of oat oil,MCT, propylene glycol, methyl & propyl parabens, benzyl OH, lecithin,testosterone and vinpocetine and heating the mixture to 130-140° F. andmixing until all the ingredients dissolve.

Emulsion Phase was prepared by mixing the water and oil followed bycooling the emulsion.

EXAMPLE 3

Preparation of COQ10 Formulation

Appropriate quantities of the raw materials were weighed for the 1.1 Kgbatch as shown below:

mg/ mg/ Ingredient (Oil) serving %/serving batch MCT (Neobee M-5) (OilPhase) 311 31.1 31100 Oat Oil (Oil Phase) 151 15.1 15100 Water 231 23.123100 Propylene Glycol (In Oil Phase) 83 8.3 8300 K-Sorbate (Preserves)(Water phase) 2 0.2 200 Na-Benzoate (Preserves) (Water phase) 2 0.2 200Polymer (PEG 400 DS) (Oil Phase) 20 2 2000 Methyl Paraben (OilPreserves) 1 0.1 100 Propyl Paraben (Oil Preserves) 1 0.1 100 Lecithin(Ultralec-P, Phospholipids) 15 1.5 1500 (Oil Phase) Polysorbate-80(Lipids) (In water 36 3.6 3600 Phase) Benzyl OH (Sterilizer,preservative) 5 0.5 500 (Oil Phase) COQ10 30 3 3000 (Lactoferrin 94%minimum) (Water 100 10 10000 phase) Sucralose (At the end) 3 0.3 300Nat. Banana (BA-133) (At the end) 5 0.5 500 Nat & Art. Vanilla (L-10181)3 0.3 300 (At the end) Totals 1000.000 100.0000 110000

Water phase was prepared by weighing appropriate quantities of water,preservatives, polysorbate 80, and lactoferrin mixing the ingredients todissolve all the components at 98-100° F.

Oil phase was prepared by weighing the appropriate amounts of oat oil,MCT, propylene glycol, methyl & propyl parabens, benzyl OH, lecithin,and COQ10 and heating the mixture to 110° F. and mixing until all theingredients dissolve.

Emulsion Phase was prepared by adding the oil and water phase followedby cooling the emulsion and addition of flavoring agents.

EXAMPLE 4

Preparation of Insulin Formulation

Appropriate quantities of the raw materials were weighed for the 0.053Kg batch as shown below:

Ingredient (Oil) mg/serving %/serving mg/batch MCT (Neobee M-5) (OilPhase) 65 13.00001 6500 Oat Oil (Oil Phase) 39.9375 7.987506 3993.75Water (Water phase) 162.559 32.511824 16255.9 Propylene Glycol (In OilPhase) 53.25 10.650008 5325 K-Sorbate (Preserves) (Water phase) 0.6656250.1331251 66.5625 Na-Benzoate (Preserves) (Water phase) 0.6656250.1331251 66.5625 Methyl Paraben (Oil Preservative) 0.665625 0.133125166.5625 Propyl Paraben (Oil Preservative) 0.665625 0.1331251 66.5625LIPOID 100 S 100 (94% 48 9.6000072 4800 Phosphatidycholine (PC)) PowderPolysorbate-80 (Lipids) (In water Phase) 66.5625 13.31251 6656.25 BenzylOH (Sterilizer, preservative) 3.328125 0.6656255 332.8125 (Oil Phase)Human Recombinant Insulin (Sigma 5.1 1.0200008 510 Aldrich) (Lactoferrin94% minimum) (Water phase) 47.5 9.5000071 4750 Triethanolamine (TEA)Water Phase 4 0.8000006 400 (add before Insulin) Triethanolamine (TEA)Oil Phase 2.1 0.4200003 210 Totals 500.000 100.0000 53177.16012

Water phase was prepared by weighing appropriate quantities of water,K-Sorbate, Na benzoate, Polysorbate-80 and triethanolamine was added anddissolved by mixing with a high speed mixer. The solution was maintainedat pH 8.00-8.35 and temperature 115° F. Oil phase was prepared in a 600mL Pyrex beaker. Appropriate quantities of oat oil, MCT, propyleneglycol, methyl paraben, propyl paraben, Benzyl OH, Lipoid S100 andtriethanolamine were added and the mixture was heated up to 115° F. todissolve the ingredients. Emulsion Phase was prepared by mixing the oiland water phase at 115° F., followed by cooling the emulsion and addingadditional water to match the volume/weight to the total batch size. Theemulsion was sheared at 2000 rpm at 115° F. until it began to thicken.

EXAMPLE 5

Preparation of Anti-Depression Formulation

Appropriate quantities of the raw materials were weighed for the 1.1 Kgbatch as shown below:

Ingredient (Oil) mg/serving %/serving mg/batch MCT (Oil Phase) 93011.625 34875 Oat Oil (Oil Phase) 330 4.125 12375 Water 3967.2 49.59148770 Propylene Glycol (In Oil 742.8 9.285 27855 Phase) K-Sorbate 60.075 225 Na-Benzoate 6 0.075 225 Salidizer (In Oil Phase) 15 0.1875562.5 Carmine Red (at the 34 0.425 1275 beginning) Polymer DS (PEG400DS) 170 2.125 6375 Methyl Paraben (Oil Phase) 3 0.0375 112.5 PropylParaben (Oil Phase) 3 0.0375 112.5 Lecithin (Oil Phase) 40 0.5 1500 Span60 (Oil Phase) 40 0.5 1500 PS-80 (In Oil) 190 2.375 7125 Phycamine 85010.625 31875 Graviola (10:1) 200 2.5 7500 L-5-HTP 150 1.875 5625Vinpocetine (Oil Phase) 8 0.1 300 Non-denatured whey protein 50 0.6251875 powder BOH (Oil Phase) 35 0.4375 1312.5 Sucralose 76 0.95 2850 NatSpearmint (MI-110) 154 1.925 5775 Totals 8000.000 100.0000 330000.0

Water phase was prepared in a 600 mL Pyrex beaker. Appropriate amount ofwater, preservatives, color, L-5 HTP, phycomine, graviola (10:1) wereadded and dissolved by mixing with a slow speed mixer. Non-denaturedwhey protein was added and mixed while maintaining the temperature at120° F. Oil phase was prepared in a 600 mL Pyrex beaker. Appropriatequantities of oils, propylene glycol, PS-80, methyl and propyl parabens,PEG, lecithin were added and mixed to dissolve the ingredients followedby addition of vinpocetine and Salidizer® at 120° F. Emulsion Phase wasprepared by adding the oil and water phase at 120° F., followed bycooling the emulsion to 95° F. and adding flavoring agents.

EXAMPLE 6

Preparation of Non-Denatured Whey Protein Formulation

Appropriate quantities of the raw materials were weighed for the 1.1 Kgbatch as shown below:

Ingredient (Oil) mg/serving %/serving mg/batch Water 15409 51.36333333564996.67 Non-denatured whey 11000 36.66666667 403333.33 protein NaBenzoate 78 0.26 2860 K-Sorbate 78 0.26 2860 Antifoam 322 1.07333333311806.667 Oat Oil 965 3.216666667 35383.333 Propylene Glycol 285 0.9510450 Methyl Paraben 30 0.1 1100 Propyl Paraben 30 0.1 1100 PEG-400 6282.093333333 23026.667 Lecithin 400 1.333333333 14666.667 Span 60 69 0.232530 Benzyl OH 142 0.473333333 5206.6667 PS-80 164 0.546666667 6013.3333Sucralose Powder 97 0.323333333 3556.6667 Nat. Fudge (CT-151) 1580.526666667 5793.3333 Nat. Chocolate (CT-147) 145 0.483333333 5316.6667Totals (+3.0% of Active) 30000 100.0000 1100000

Water phase was prepared in a 1500 mL Pyrex beaker. Appropriate amountsof water, K-Sorbate, Na benzoate, Carmine red, and Polysorbate-80 wereadded and dissolved by mixing with a slow speed mixer. Non-denaturedwhey protein and anti-foam was mixed at pH 6.80 and a temperature of115° F. Oil phase was prepared in a 600 mL Pyrex beaker. Appropriatequantities of oat oil, propylene glycol, PEG-400, methyl paraben, propylparaben, lecithin, and span 60 were added and the mixture was heated upto 115° F. to dissolve the ingredients. Emulsion Phase was prepared byadding the oil and water phase at 115° F., followed by cooling theemulsion and adding flavoring agents.

In Examples 7-12, the amount of each ingredient needed to achieve theindicated amount/serving was calculated based on the specific gravity ofthe final composition.

EXAMPLE 7

Preparation of CoQ10 formulation

Appropriate quantities of the raw materials were weighed for the 1.3 Kgbatch as shown below:

Amount Ingredient (Oil) mg/serv. needed (mg) %/serving mg/batch MCT(Neobee M-5) (Oil Phase) 55 57.695 11.0000 144237.5 Oat Oil (Oil Phase)39.9375 41.8944375 7.9875 104736.1 Water (Water phase) 155.909163.548541 31.1818 408871.4 Propylene Glycol (In Oil Phase) 45 47.2059.0000 118012.5 K-Sorbate (Preserves) (Water phase) 0.665625 0.698240630.1331 1745.602 Na-Benzoate (Preserves) (Water phase) 0.6656250.69824063 0.1331 1745.602 Methyl Paraben (Oil Preservative) 0.6656250.69824063 0.1331 1745.602 Propyl Paraben (Oil Preservative) 0.6656250.69824063 0.1331 1745.602 LIPOID 100 S 100 (94% 48 50.352 9.6000 125880Phosphatidycholine (PC)) Powder Polysorbate-80 (Lipids) (In water Phase)66.5625 69.8240625 13.3125 174560.2 Benzyl OH (Sterilizer, preservative)(Oil 3.328125 3.49120313 0.6656 8728.008 Phase) COQ10 (Oil Phase) 3031.47 6.0000 78675 (Lactoferrin 94% minimum) (Water 47.5 49.8275 9.5000124568.8 phase) Triethanolamine (TEA) Water Phase (add 4 4.196 0.800010490 before Insulin) Triethanolamine (TEA) Oil Phase 2.1 2.2029 0.42005507.25 Totals 500.000 524.500 100.0000 1311249.0

Procedure # Phase pH Temp ° C. Step (1) PS-80/H20/TEA 8.61 45.4 Step (2)PS-80/IGF-1 8.3 42.1 Step (3) PS-80/Lactof 8.11 43.7 Step (4) QualityControl 8.34 24.51. Oil phase: Oil phase was prepared first as follows:

Equipment used: Corning Hot Plate, IKA mixer type RE16 S1 serial No93-133-35, 600 mL Pyrex Beaker.

Ingredients were added in the following order: Oat Oil, MCT, propyleneglycol, methyl and propyl parabens, benzyl OH and TEA. The mixture washeated to 115° F., and mixed at 250 rpm to dissolve the ingredients.Phosphatidylcholine (lipoid S100) was added at 115° F. at 250 rpm andmixed to dissolve. CoQ10 was added to the mixture and dissolved to alight orange color.

2. Water phase: Water phase was prepared as follows:

Equipment used: Corning Hot Plate, Arde Barinco Mixer Type 74D serial NoL-1274, 1500 ml Pyrex Beaker, Hanna Instruments pH meter model HI 8314.

Ingredients were added in the following order: water, K-Sorbate, NaBenzoate, Polysorbate 80, and TEA. The pH was maintained at >8.30.Solution was heated slowly and stirred with a stirring rod until all thePS-80 was dissolved into the solution (straw yellow color). Temperaturewas maintained at 115° F. and pH at above 8.30, adjusting with TEA asneeded. Lactoferrin was added to the straw-yellow solution while mixingwith the Arde Barinco Mixer at 10% RPM on Forward. Temperature wasmaintained at 115° F. and the mixer at 10% of RPM until a gooddispersion was observed. Antifoam was added as needed. All lactoferrinwas dissolved until there were no clumps in the solution.

3. Emulsion phase: Emulsion phase was prepared as follows:

Equipment used: Arde Barinco Mixer Type 74D serial No L-1274

Oil phase was added to water phase (each at 115° F.) at 14% of RPM for10 minutes while cooling. After 10 minutes, the mixing speed was loweredto 10% RPM. Mixing was continued with Arde Barinco mixer whilemaintaining enough shear for the emulsion and the mixture was cooledduring the process.

4. Finished product: The finished product had a pH above 8.00 and wastested for amount of CoQ 10 present.

EXAMPLE 8

Preparation of Oratropin-1 Formulation

Appropriate quantities of the raw materials were weighed for the 1.3 Kgbatch as shown below:

Amount Ingredient (Oil) mg/serv. needed (mg) %/serving mg/batch MCT(Neobee M-5) (Oil Phase) 65 68.185 13.0000 170462.5 Oat Oil (Oil Phase)39.9375 41.8944375 7.9875 104736.1 Water (Water phase) 167.619175.832331 33.5238 439580.8 Propylene Glycol (In Oil Phase) 53.2555.85925 10.6500 139648.1 K-Sorbate (Preserves) (Water phase) 0.6656250.69824063 0.1331 1745.602 Na-Benzoate (Preserves) (Water phase)0.665625 0.69824063 0.1331 1745.602 Methyl Paraben (Oil Preservative)0.665625 0.69824063 0.1331 1745.602 Propyl Paraben (Oil Preservative)0.665625 0.69824063 0.1331 1745.602 LIPOID 100 S 100 (94%Phosphatidycholine 48 50.352 9.6000 125880 (PC)) Powder Polysorbate-80(Lipids) (In water Phase) 66.5625 69.8240625 13.3125 174560.2 Benzyl OH(Sterilizer, preservative) (Oil 3.328125 3.49120313 0.6656 8728.008Phase) IGF-1 0.04 0.04196 0.0080 104.9 (Lactoferrin 94% minimum) (Waterphase) 47.5 49.8275 9.5000 124568.8 Triethanolamine (TEA) Water Phase(add 4 4.196 0.8000 10490 before Insulin) Triethanolamine (TEA) OilPhase 2.1 2.2029 0.4200 5507.25 Totals 500.000 524.500 100.00001311249.0

Procedure # Phase pH Temp ° C. Step (1) PS-80/H20/TEA 8.61 45.4 Step (2)PS-80/IGF-1 8.3 42.1 Step (3) PS-80/Lactof 8.11 43.7 Step (4) QualityControl 8.34 24.51. Oil phase: Oil phase was prepared first as follows:

Equipment used: Corning Hot Plate, IKA mixer type RE16 S1 serial No93-133-35, 600 ml Pyrex Beaker.

Ingredients were added in the following order: Oat Oil, MCT, propyleneglycol, methyl and propyl parabens, benzyl OH and TEA. The mixture washeated to 115° F., and mixed at 250 RPM to dissolve the ingredients.Phosphatidylcholine (lipoid S100) was added at 115° F. at 250 RPM andmixed to dissolve.

2. Water phase: Water phase was prepared as follows:

Equipment used: Corning Hot Plate, Arde Barinco Mixer Type 74D serial NoL-1274, 1500 ml Pyrex Beaker, Hanna Instruments pH meter model HI 8314.

Ingredients were added in the following order: water, K-Sorbate, NaBenzoate, Polysorbate 80, and TEA. The pH was maintained at >8.30.Solution was heated slowly and stirred with a stirring rod until all thePS-80 was dissolved into the solution (straw yellow color). Temperaturewas maintained at 115° F. pH was maintained at above 8.30, adjustingwith TEA as needed. IGF-1 was added to the straw-yellow solution, whilemaintaining temperature at 115° F. and pH at 8.30. Lactoferrin was addedwith the Arde Barinco Mixer at 10% RPM on Forward. Temperature wasmaintained at 115° F. and the mixer at 10% of RPM until a gooddispersion was observed. Antifoam was added as needed. All lactoferrinwas dissolved so that the solution did not contain any lumps.

3. Emulsion phase: Emulsion phase was prepared as follows:

Equipment used: Arde Barinco Mixer Type 74D serial No L-1274

Oil phase was added to water phase (each at 115° F.) at 14% of RPM for10 minutes while cooling. After 10 minutes the mixing speed was loweredto 10% RPM. Mixing was continued with Arde Barinco mixer whilemaintaining enough shear for the emulsion and the mixture was cooledduring the process.

4. Finished product: The finished product had a pH above 8.00 and wastested for the amount of IGF-1.

EXAMPLE 9

Preparation of Hexatropin-6 Formulation

Appropriate quantities of the raw materials were weighed for the 1.3 Kgbatch as shown below:

Amount Ingredient (Oil) mg/serv. needed (mg) %/serving mg/batch MCT(Neobee M-5) (Oil Phase) 65 68.185 13.0000 170462.5 Oat Oil (Oil Phase)39.9375 41.8944375 7.9875 104736.1 Water (Water phase) 167.459175.664491 33.4918 439161.2 Propylene Glycol (In Oil Phase) 53.2555.85925 10.6500 139648.1 K-Sorbate (Preserves) (Water phase) 0.6656250.69824063 0.1331 1745.602 Na-Benzoate (Preserves) (Water phase)0.665625 0.69824063 0.1331 1745.602 Methyl Paraben (Oil Preservative)0.665625 0.69824063 0.1331 1745.602 Propyl Paraben (Oil Preservative)0.665625 0.69824063 0.1331 1745.602 LIPOID 100 S 100 (94%Phosphatidycholine 48 50.352 9.6000 125880 (PC)) Powder Polysorbate-80(Lipids) (In water Phase) 66.5625 69.8240625 13.3125 174560.2 Benzyl OH(Sterilizer, preservative) (Oil 3.328125 3.49120313 0.6656 8728.008Phase) Hexarelin 0.1 0.1049 0.0200 262.25 GHRP-6 (Growth HormonePeptide-6) 0.1 0.1049 0.0200 262.25 Agonist (Lactoferrin 94% minimum)(Water phase) 47.5 49.8275 9.5000 124568.8 Triethanolamine (TEA) WaterPhase (add 4 4.196 0.8000 10490 before Insulin) Triethanolamine (TEA)Oil Phase 2.1 2.2029 0.4200 5507.25 Totals 500.000 524.500 100.00001311249.0

Procedure # Phase pH Temp ° C. Step (1) PS-80/H20/TEA 8.61 45.4 Step (2)PS-80/Hex/GHRP-6 8.3 42.1 Step (3) PS-80/Lactof 8.11 43.7 Step (4)Quality Control 8.34 24.51. Oil phase: Oil phase was prepared first as follows:

Equipment used: Corning Hot Plate, IKA mixer type RE16 S1 serial No93-133-35, 600 ml Pyrex Beaker

Ingredients were added in the following order: Oat Oil, MCT, propyleneglycol, methyl and propyl parabens, benzyl OH and TEA. The mixture washeated to 115° F., and mixed at 250 RPM to dissolve the ingredients.Phosphatidylcholine (lipoid S100) was added at 115° F. at 250 RPM andmixed to dissolve.

2. Water phase: Water phase was prepared as follows:

Equipment used: Corning Hot Plate, Arde Barinco Mixer Type 74D serial NoL-1274, 1500 ml Pyrex Beaker, Hanna Instruments pH meter model HI 8314.

Ingredients were added in the following order: water, K-Sorbate, NaBenzoate, Polysorbate 80 (PS-80), and TEA. The pH was maintainedat >8.30. Solution was heated slowly and stirred with a stirring roduntil all the PS-80 was dissolved into the solution (straw yellowcolor). Temperature was maintained at 115° F. and pH at above 8.30,adjusting with TEA as needed. Hexarelin & GHRP-6 agonist were added at115° F. pH was maintained at above 8.30. Lactoferrin was added to thesolution while mixing with the Arde Barinco Mixer at 10% RPM on Forward.Temperature was maintained at 115° F. and the mixer at 10% of RPM untila good dispersion was observed. Antifoam was added as needed. Alllactoferrin was dissolved until there were no clumps in the solution.

3. Emulsion phase: Emulsion phase was prepared as follows:

Equipment used: Arde Barinco Mixer Type 74D serial No L-1274

Oil phase was added to water phase (each at 115° F.) at 14% of RPM for10 minutes while cooling. After 10 minutes the mixing speed was loweredto 10% RPM. Mixing was continued with Arde Barinco mixer whilemaintaining enough shear for the emulsion and the mixture was cooledduring the process.

4. Finished product: The finished product has a pH above 8.00 was testedfor contents of GHRP-6 agonist and Hexarelin.

EXAMPLE 10

Preparation of Insulin-Albumin Formulation

Appropriate quantities of the raw materials were weighed for the 0.11 Kgbatch as shown below:

Amount Ingredients Mg/serv. needed (mg) %/serving mg/batch MCT (NeobeeM-5) (Oil Phase) 65 68.185 13.0046 13637 Oat Oil (Oil Phase) 39.937541.8944375 7.9903 8378.8875 Water (Water phase) 150.597 157.97625330.1300 31595.2506 Propylene Glycol (In Oil Phase) 53.25 55.8592510.6538 11171.85 K-Sorbate (Preserves) (Water phase) 0.6656250.698240625 0.1332 139.648125 Na-Benzoate (Preserves) (Water phase)0.665625 0.698240625 0.1332 139.648125 Methyl Paraben (Oil Preservative)0.665625 0.698240625 0.1332 139.648125 Propyl Paraben (Oil Preservative)0.665625 0.698240625 0.1332 139.648125 LIPOID 100 S 100 (94% 48 50.3529.6034 10070.4 Phosphatidycholine (PC)) Powder Polysorbate-80 (Lipids)(In water 66.5625 69.8240625 13.3172 13964.8125 Phase) Benzyl OH(Sterilizer, preservative) 3.328125 3.491203125 0.6659 698.240625 (OilPhase) Human Recombinant Insulin (Sigma 10 11 2.0980 2200 Aldrich)(Albumin) (Water phase) 47.5 49.8275 9.5033 9965.5 Triethanolamine (TEA)Water Phase 10.4 10.9096 2.0807 2181.92 (add before Insulin)Triethanolamine (TEA) Oil Phase 2.1 2.2029 0.4201 440.58 Totals 499.338524.315 100.0000 104863.0337

Procedure Phase pH Temp ° C. Step (1) PS-80/H20/TEA 8.61 45.4 Step (2)PS-80/Insulin 8.3 42.1 Step (3) PS-80/Albumin 8.27 43.7 Step (4)Finished Product 8.42 13.61. Oil phase: Oil phase was prepared first as follows:

Equipment used: Corning Hot Plate, IKA mixer type RE16 S1 serial No93-133-35, 80 ml Pyrex Beaker.

Ingredients were added in the following order: Oat Oil, MCT, propyleneglycol, methyl and propyl parabens, benzyl OH and TEA. The mixture washeated to 115° F., and mixed at 250 RPM to dissolve the ingredients.Phosphatidylcholine (lipoid S100) was added at 115° F. at 250 RPM andmixed to dissolve. COQ10 was added to the mixture and dissolved to alight orange color.

2. Water phase: Water phase was prepared as follows:

Equipment used: Corning Hot Plate, Arde Barinco Mixer Type 74D serial NoL-1274, 250 ml Pyrex Beaker, Hanna Instruments pH meter model HI 8314.

Ingredients were added in the following order: water, K-Sorbate, NaBenzoate, Polysorbate 80, and TEA. The pH was maintained at >8.30.Solution was heated slowly and stirred with a stirring rod until all thePS-80 was dissolved into the solution (straw yellow color). Temperaturewas maintained at 115° F. and pH at above 8.30, adjusting with TEA asneeded. Insulin was added to the straw-yellow solution, whilemaintaining temperature at 115° F. and pH at 8.30. Albumin was addedwith the Arde Barinco Mixer at 10% RPM on Forward. Temperature wasmaintained at 115° F. and the mixer at 10% of RPM until a gooddispersion was observed. Antifoam was added as needed. All lactoferrinwas dissolved so that the solution did not contain any lumps.

3. Emulsion phase: Emulsion phase was prepared as follows:

Equipment used: Arde Barinco Mixer Type 74D serial No L-1274

Oil phase was added to water phase (each at 115° F.) at 14% of RPM for10 minutes while cooling. After 10 minutes the mixing speed was loweredto 10% RPM. Mixing was continued with Arde Barinco mixer whilemaintaining enough shear for the emulsion and the mixture was cooledduring the process.

4. Finished product: The finished product had a pH above 8.00 and wastested for the amount of insulin.

EXAMPLE 11

Preparation of Insulin-Lactoferrin Formulation

Appropriate quantities of the raw materials were weighed for the 0.53 Kgbatch as shown below:

Amount Ingredients mg/serv. needed %/serving mg/batch MCT (Neobee M-5)(Oil Phase) 65 68.185 12.9865 68185 Oat Oil (Oil Phase) 39.937541.8944375 7.9792 41894.4375 Water (Water phase) 150.597 157.97625330.0882 157976.253 Propylene Glycol (In Oil Phase) 53.25 55.8592510.6390 55859.25 K-Sorbate (Preserves) (Water phase) 0.6656250.698240625 0.1330 698.240625 Na-Benzoate (Preserves) (Water phase)0.665625 0.698240625 0.1330 698.240625 Methyl Paraben (Oil Preservative)0.665625 0.698240625 0.1330 698.240625 Propyl Paraben (Oil Preservative)0.665625 0.698240625 0.1330 698.240625 LIPOID 100 S 100 (94%Phosphatidycholine 48 50.352 9.5901 50352 (PC)) Powder Polysorbate-80(Lipids) (In water Phase) 66.5625 69.8240625 13.2987 69824.0625 BenzylOH (Sterilizer, preservative) (Oil 3.328125 3.491203125 0.66493491.203125 Phase) Human Recombinant Insulin (Sigma 10.66211711.72832925 2.2338 11728.32925 Aldrich) (Lactoferrin 94% minimum“transferring”) 47.5 49.8275 9.4902 49827.5 (Water phase)Triethanolamine (TEA) Water Phase (add 10.4 10.9096 2.0778 10909.6before Insulin) Triethanolamine (TEA) Oil Phase 2.1 2.2029 0.4196 2202.9Totals 500.000 525.043 100.0000 525043.4979

Procedure # Phase pH Temp ° C. Step (1) PS-80/H20/TEA 8.61 45.4 Step (2)PS-80/Insulin 8.3 42.1 Step (3) PS-80/Lactof 8.27 43.7 Step (4) FinishedProduct 8.42 13.61. Oil phase: Oil phase was prepared first as follows:

Equipment used: Corning Hot Plate, IKA mixer type RE16 S1 serial No93-133-35, 250 ml Pyrex Beaker

Ingredients were added in the following order: Oat Oil, MCT, propyleneglycol, methyl and propyl parabens, benzyl OH and TEA. The mixture washeated to 115° F., and mixed at 250 RPM to dissolve the ingredients.Phosphatidylcholine (lipoid S 100) was added at 115° F. at 250 RPM andmixed to dissolve.

2. Water phase: Water phase was prepared as follows:

Equipment used: Corning Hot Plate, Arde Barinco Mixer Type 74D serial NoL-1274, 600 ml Pyrex Beaker, Hanna Instruments pH meter model HI 8314

Ingredients were added in the following order: water, K-Sorbate, NaBenzoate, Polysorbate 80, and TEA. The pH was maintained at >8.30.Solution was heated slowly and stirred with a stirring rod until all thePS-80 was dissolved into the solution (straw yellow color). Temperaturewas maintained at 115° F. and pH at above 8.30, adjusting with TEA asneeded. Insulin was added to the straw-yellow solution, whilemaintaining temperature at 115° F. and pH at 8.30. Lactoferrin was addedwith the Arde Barinco Mixer at 10% RPM on Forward. Temperature wasmaintained at 115° F. and the mixer at 10% of RPM until a gooddispersion was observed. Antifoam was added as needed. All lactoferrinwas dissolved so that the solution did not contain any lumps.

3. Emulsion phase: Emulsion phase was prepared as follows:

Equipment used: Arde Barinco Mixer Type 74D serial No L-1274

Oil phase was added to the water phase (each at 115° F.) at 14% of RPMfor 10 minutes while cooling. After 10 minutes the mixing speed waslowered to 10% RPM. Mixing was continued with Arde Barinco mixer whilemaintaining enough shear for the emulsion and the mixture was cooledduring the process.

4. Finished product: The finished product had a pH above 8.00 and wastested for the amount of insulin.

EXAMPLE 12

Preparation of Insulin-Lactoferrin Formulation

Appropriate quantities of the raw materials were weighed for the 0.65 Kgbatch as shown below:

Amount Ingredients mg/serv. needed %/serving mg/batch MCT (Neobee M-5)(Oil Phase) 65 84.5 13.0428 84500 Oat Oil (Oil Phase) 39.9375 51.918758.0138 51918.75 Water (Water phase) 150.597 195.7761 30.2186 195776.1Propylene Glycol (In Oil Phase) 53.25 69.225 10.6851 69225 K-Sorbate(Preserves) (Water phase) 0.665625 0.8653125 0.1336 865.3125 Na-Benzoate(Preserves) (Water phase) 0.665625 0.8653125 0.1336 865.3125 MethylParaben (Oil Preservative) 0.665625 0.8653125 0.1336 865.3125 PropylParaben (Oil Preservative) 0.665625 0.8653125 0.1336 865.3125 LIPOID 100S 100 (94% Phosphatidycholine 48 62.4 9.6316 62400 (PC)) PowderPolysorbate-80 (Lipids) (In water Phase) 66.5625 86.53125 13.356386531.25 Benzyl OH (Sterilizer, preservative) (Oil Phase) 3.3281254.3265625 0.6678 4326.5625 Human Recombinant Insulin (Sigma Aldrich)10.662117 11.72832925 1.8103 11728.32925 (Lactoferrin 94% minimum“transferring”) (Water 47.5 61.75 9.5313 61750 phase) Triethanolamine(TEA) Water Phase (add before 10.4 13.52 2.0868 13520 Insulin)Triethanolamine (TEA) Oil Phase 2.1 2.73 0.4214 2730 Totals 500.000647.867 100.0000 647867.2417

Procedure # Phase pH Temp ° C. Step (1) PS-80/H20/TEA 8.61 45.4 Step (2)PS-80/Insulin 8.3 42.1 Step (3) PS-80/Lactof 8.27 43.7 Step (4) FinishedProduct 8.42 13.61. Oil phase: Oil phase was prepared first as follows:

Equipment used: Corning Hot Plate, IKA mixer type RE16 S1 serial No93-133-35, 600 ml Pyrex Beaker

Ingredients were added in the following order: Oat Oil, MCT, propyleneglycol, methyl and propyl parabens, benzyl OH and TEA. The mixture washeated to 115° F., and mixed at 250 RPM to dissolve the ingredients.Phosphatidylcholine (lipoid S100) was added at 115° F. at 250 RPM andmixed to dissolve.

2. Water phase: Water phase was prepared as follows:

Equipment used: Corning Hot Plate, Arde Barinco Mixer Type 74D serial NoL-1274, 250 ml Pyrex Beaker, Hanna Instruments pH meter model HI 8314

Ingredients were added in the following order: water, K-Sorbate, NaBenzoate, Polysorbate 80, and TEA. The pH was maintained at >8.30.Solution was heated slowly and stirred with a stirring rod until all thePS-80 was dissolved into the solution (straw yellow color). Temperaturewas maintained at 115° F. and pH at above 8.30, adjusting with TEA asneeded. Insulin was added to the straw-yellow solution, whilemaintaining temperature at 115° F. and pH at 8.30. Lactoferrin was addedwhile mixing the solution with the Arde Barinco Mixer at 10% RPM onForward. Temperature was maintained at 115° F. and the mixer at 10% ofRPM until a good dispersion was observed. Antifoam was added as needed.All lactoferrin was dissolved so that the solution did not contain anylumps.

3. Emulsion phase: Emulsion phase was prepared as follows:

Equipment used: Arde Barinco Mixer Type 74D serial No L-1274

Oil phase was added to water phase (each at 115° F.) at 14% of RPM for10 minutes while cooling. After 10 minutes the mixing speed was loweredto 10% RPM. Mixing was continued with Arde Barinco mixer whilemaintaining enough shear for the emulsion and the mixture was cooledduring the process.

4. Finished product: The finished product had a pH above 8.00 and wastested for the amount of insulin.

EXAMPLE 13

Preparation of Insulin-Immunoglobulin Formulation

Appropriate quantities of the raw materials were weighed for the 0.11 Kgbatch as shown below:

Amount Ingredients mg/serv. needed %/serving mg/batch MCT (Neobee M-5)(Oil Phase) 65 68.185 13.0046 13637 Oat Oil (Oil Phase) 39.937541.8944375 7.9903 8378.8875 Water (Water phase) 150.597 157.97625330.1300 31595.2506 Propylene Glycol (In Oil Phase) 53.25 55.8592510.6538 11171.85 K-Sorbate (Preservs) (Water phase) 0.665625 0.6982406250.1332 139.648125 Na-Benzoate (Preservs) (Water phase) 0.6656250.698240625 0.1332 139.648125 Methyl Paraben (Oil Preservative) 0.6656250.698240625 0.1332 139.648125 Propyl Paraben (Oil Preservative) 0.6656250.698240625 0.1332 139.648125 LIPOID 100 S 100 (94% Phosphatidycholine(PC)) Powder 48 50.352 9.6034 10070.4 Polysorbate-80 (Lipids) (In waterPhase) 66.5625 69.8240625 13.3172 13964.8125 Benzyl OH (Sterilizer,preservatizer) (Oil Phase) 3.328125 3.491203125 0.6659 698.240625 HumanRecombinant Insulin (Sigma Aldrich) 10 11 2.0980 2200 IGG(Immunoglobulin) (Water phase) 47.5 49.8275 9.5033 9965.5Triethanolamine (TEA) Water Phase (add before Insulin) 10.4 10.90962.0807 2181.92 Triethanolamine (TEA) Oil Phase 2.1 2.2029 0.4201 440.58Totals 499.338 524.315 100.0000 104863.0337

Procedure # Phase pH Temp ° C. Step (1) PS-80/H20/TEA 8.61 45.4 Step (2)PS-80/Insulin 8.3 42.1 Step (3) PS-80/IGG 8.27 43.7 Step (4) FinishedProduct 8.42 13.61. Oil phase: Oil phase was prepared first as follows:

Equipment used: Corning Hot Plate, IKA mixer type RE16 S1 serial No93-133-35, 80 ml Pyrex Beaker.

Ingredients were added in the following order: Oat Oil, MCT, propyleneglycol, methyl and propyl parabens, benzyl OH and TEA. The mixture washeated to 115° F., and mixed at 250 RPM to dissolve the ingredients.Phosphatidylcholine (lipoid S 100) was added at 115° F. at 250 RPM andmixed to dissolve.

2. Water phase: Water phase was prepared as follows:

Equipment used: Corning Hot Plate, Arde Barinco Mixer Type 74D serial NoL-1274, 250 ml Pyrex Beaker, Hanna Instruments pH meter model HI 8314.

Ingredients were added in the following order: water, K-Sorbate, NaBenzoate, Polysorbate 80, and TEA. The pH was maintained at >8.30.Solution was heated slowly and stirred with a stirring rod until all thePS-80 was dissolved into the solution (straw yellow color). Temperaturewas maintained at 115° F. and pH at above 8.30, adjusting with TEA asneeded. Insulin was added to the straw-yellow solution, whilemaintaining temperature at 115° F. and pH at 8.30. Immunoglobulin wasadded with the Arde Barinco Mixer at 10% RPM on Forward. Temperature wasmaintained at 115° F. and the mixer at 10% of RPM until a gooddispersion was observed. Antifoam was added as needed. Allimmunoglobulin was dissolved so that the solution did not contain anylumps.

3. Emulsion phase: Emulsion phase was prepared as follows:

Equipment used: Arde Barinco Mixer Type 74D serial No L-1274

Oil phase was added to water phase (each at 115° F.) at 14% of RPM for10 minutes while cooling. After 10 minutes the mixing speed was loweredto 10% RPM. Mixing was continued with Arde Barinco mixer whilemaintaining enough shear for the emulsion and the mixture was cooledduring the process.

4. Finished product: The finished product had a pH above 8.00 and wastested for the amount of insulin.

EXAMPLE 14

Oral Bioavailability and Pharmacokinetic Studies in Dogs

Oral bioavailability of insulin composition was determined using an IVstudy followed by an oral crossover study and the relative areas ofunder the curve, plasma half life, C_(max), and T_(max) was calculated.

Protocol Outline

Mongrel dogs (20-30 kg) were used (n=2) for the study. The dogs werefasted overnight for both the studies in order to achieve baselineglucose and insulin levels.

IV Study: IV injection of 0.01 mg/kg human insulin was administered tothe dogs. Blood samples were taken at: 2, 5, 10, 15, 20, 25, 40, 60,120, 180, and 240 minutes. Blood was analyzed for glucose and insulinlevels for all time points.

Oral Study: 4 days were allowed for washout following the IV study.Insulin composition of Example 12 was orally administered between lipsand gums at a dose of 0.02 mg/kg. Blood samples were taken at 5, 5.5,6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 16, and 24 hoursand analyzed for insulin and glucose levels.

Following data collection, plasma concentration, plasma half-life, peakconcentration (C_(max)) and time to reach C. (t_(max)) were determined.From the areas under the curve, percent oral bioavailability wasdetermined.

TABLE 1 DOG # 71, Weight of dog = 22 kg, IV dosing: DOSE = 0.01 mg/kgTime Plasma Insulin Plasma Glucose (min) (ng/mL) (mg/dL) 2 50.2 89 526.6 82 10 15.9 57 15 10.1 46 20 7.6 41 25 5.9 42 40 2.5 39 60 1.2 48120 0.19 69 180 0.08 87 240 0.08 86

TABLE 2 DOG 71, Weight of dog = 22 kg P.O dosing: DOSE = 0.02 mg/kgPlasma Insulin Plasma Time (h) ng/mL Glucose 5 0.17 80 5.5 0.02 76 6 079 6.5 0.06 86 7 0.2 84 7.5 0.1 85 8 0.46 85 8.5 0.23 85 9 0.13 84 9.50.45 85 10 1.1 88 10.5 0.42 99 11 0.68 88 11.5 0.68 100 12 0.38 82 160.55 85 24 0.5 87

TABLE 3 DOG # 72, Weight of dog = 28 kg, IV dosing: DOSE = 0.01 mg/kgTime Plasma Insulin Plasma Glucose (min) (ng/mL) (mg/dL) 2 27.3 89 521.4 60 10 11.4 31 15 6.5 28 20 3.4 35 25 2.7 24 40 0.7 21 60 0.2 33 1200.04 68 180 0 102 240 0.04 99

TABLE 4 DOG # 72, Weight of dog = 28 kg, P.O. dosing: DOSE = 0.02 mg/kgPlasma Insulin Plasma Glucose Time (h) (ng/mL) (mg/dL) 5 0.17 82 5.50.02 97 6 0 89 6.5 0.06 90 7 0.2 84 7.5 0.1 89 8 0.46 93 8.5 0.23 103 90.13 93 9.5 0.45 101 10 0.28 95 10.5 1.1 88 11 0.42 95 11.5 0.68 88 120.38 91 16 0.55 103 24 0.50 92

TABLE 5 PHARMACOKINETIC ANALYSIS FOR ORAL INSULIN IN DOGSMiprocelle-Insulin Analytical Range 0.01-3000/mL TTI RFA: 3021 PO Dose0.02 mg/kg Time Animal #/Concentration (hr) 71 72 Mean 5.00 0.17 0.000.85 5.50 0.02 0.05 0.04 6.00 0.00 0.02 0.01 6.50 0.06 0.12 0.09 7.000.2 0.0 0.1 7.50 0.1 0.12 0.1 8.00 0.46 0.25 0.35 8.50 0.23 0.67 0.459.00 0.13 0.05 0.09 9.50 0.45 0.06 0.25 10.00 0.28 0.34 0.62 10.50 1.101.50 1.30 11.00 0.42 0.20 0.31 11.50 0.68 0.40 1.10 12.00 0.38 0.22 0.3016.00 0.55 1.00 0.78 24.00 0.50 0.02 0.26 Pharmacokinetic EstimatesHalf-life (hr) 18.00 Tmax (hr) 10.50 Cmax (ng/mL) 1.3 AUC 0-T (hr *ng/mL) 8.9 % Bioavailability 61%

TABLE 6 INTRAVENOUS PHARMACOKINETIC ANALYSIS FOR MIPROCELLE-INSULIN INDOGS Miprocelle-Insulin Analytical Range 0.01-3000 ng/mL TTI RFA: 3021IV Dose 0.01 Animal #/ Time Concentration (ng/mL) (hr) 71 72 Mean 0.0350.2 27 −39 0.08 26.6 21 24 0.17 15.9 11.4 13.7 0.25 10.10 6.50 8.300.33 7.60 3.40 5.50 0.42 5.90 2.70 4.30 1 2.5 0.7 1.60 2 1.2 0.2 0.7 30.00 0.00 0.0 4 0.02 0.04 0.03 Half-life (hr) 0.23 Tmax (hr) 0.03 Cmax(ng/mL) 38.5 AUC 0-T (hr * ng/mL) I 7.4

EXAMPLE 15

Oral Bioavailability and Pharmacokinetic Studies in Rats

Preliminary studies for oral bioavailability and pharmacokinetics inrats were conducted with various insulin formulations (albumin-insulin(example 10), IgG-insulin (example 13) and lactoferrin-insulin (example12) were administered to rats at a volume of 0.2 mL at 230-250 mgbetween the gum and lips. The formulations were spotted throughout thegum and lip interface so they were evenly distributed. Blood sampleswere withdrawn via retro-orbital bleed at the times shown in Tables 7-8.

Control animals showed no human insulin at any time. Human insulinappeared in the blood for all treatment between 4-5 hours.

Animal Time Composition No. (h) Insulin ng/ml Glucose (mg/Dl) 3 <2.00110 4 <2.00 123 1 5 <2.00 106 14 <2.00 146 18 <2.00 164 Control 3 <2.00112 4 <2.00 116 2 5 <2.00 115 14 <2.00 18 <2.00 162 <2.00 (mean) 131(mean) 3 <2.00 113 4 <2.00 121 1 5 5.80 14 <2.00 159 18 <2.00 238Lactoferrin-insulin 3 <2.00 116 4 <2.00 111 2 5 6.40 144 14 <2.00 166 18<2.00 173 2.82 (mean) 146 (mean) 3 <2.00 124 1 4 18.10 109 5 14 <2.00150 18 <2.00 206 Albumin + insulin 3 QNS 113 4 54.00 118 2 5 <2.00 16514 QNS 115 18 <2.00 209 11.73 (mean) 143 (mean) 3 <2.00 121 4 54.70 1 5<2.00 132 14 <2.00 166 18 <2.00 278 IgG + insulin 3 <2.00 110 4 5:60 2 5<2.00 108 14 <2.00 171 18 <2.00 208 7.63 (mean) 157 (mean)

EXAMPLE 16

Studies in Human

Composition of Example 12 was administered (0.5 cc) to a human subjectfor 3 days according the following protocol and the glucose levels weremonitored.

Time Glucose Units Notes Blood Glucose-Day 1 7:30 PM 94 7:35 PM; Dinner8:15 PM 186 8:17 PM; Oral Insulin 8:29 PM 208 8:45 PM 180 9:15 PM 1669:46 PM 135 1:40 AM 103 7:00 AM 113 7:35 AM 108 Blood Glucose-Day 2 9:45AM; Oral Insulin 12:55 PM  100 1:00 PM; Lunch 1:40 PM 200 2:47 PM 1464:25 PM 103 4:53 PM 90 5:26 PM 103 6:20 PM 99 6:20 PM; Dinner 6:50 PM102 7:21 PM 112 9:10 PM 110 9:56 PM 138 10:30 PM  127 Blood Glucose-Day3 1:45 PM 103 1:50 PM; Lunch 2:25 PM 138 2:30 PM; More Food 3:02 PM 1533:25 PM 134 3:30; More Food 3:45 PM 132 3:53 PM 136 4:27 PM 138 4:46 PM150 6:17 PM 110 6:18 PM; Dinner 6:47 PM 115 7:24 PM 127 8:04 PM 108 9:45PM 158 10:35 PM  122

The comparison of data collected on day 1, 2 and 3 indicates (seeFIG. 1) that the blood glucose levels were being regulated in a moresustained manner on the third day.

Since modifications will be apparent to those of skill in this art, itis intended that this invention be limited only by the scope of theappended claims.

1. A composition, comprising: an agent for delivery; a delivery vehicleassociated with the agent, wherein: the composition is formulated as anemulsion and is formulated for mucosal delivery to the oral orgastrointestinal tract mucosa; the mucoadhesive protein is associatedwith the delivery vehicle via a chemical or physical bond; and thedelivery vehicle is selected from among a micelle, inverse micelle,liposome, cubosome and a mixture thereof; and a mucoadhesive protein,wherein: the mucoadhesive protein is present at a concentration of about1% by weight up to about 50% of the total weight of the composition; andthe mucoadhesive protein is selected from among the family oftransferrins and the family of mucin proteins, whereby the compositionadsorbs to the mucosa for effecting systemic delivery of the agent. 2.The composition of claim 1, wherein the emulsion is an oil-in-water or awater-in-oil emulsion.
 3. The composition of claim 1, wherein the agentis dissolved in the oil phase or is dissolved in the water phase.
 4. Thecomposition of claim 1, wherein the mucoadhesive protein is atransferrin protein selected from among a lactoferrin, lactoferrinbinding proteins, recombinant lactoferrin, lactoferricin, lactoferricinb, transferrin binding proteins, transferrin, ovotransferrin, neutrophilgranules, apo-lactoferrin and lanthanide-lactoferrin.
 5. The compositionof claim 1, wherein the protein is from a human or bovine source.
 6. Thecomposition of claim 1, wherein the mucoadhesive protein is lactoferrin.7. The composition of claim 1, wherein the agent alters a body functionor alters cosmetic appearance.
 8. The composition of claim 1, whereinthe agent is a therapeutic agent.
 9. The composition of claim 1, whereinthe agent is selected from among antidiabetics, anticonvulsants,analgesics, antiparkinsons, anti-inflammatories, calcium antagonists,anesthetics, antimicrobials, antimalarials, antiparasitics,antihypertensives, antihistamines, antipyretics, alpha-adrenergicagonists, alpha-blockers, biocides, bactericides, bronchial dilators,beta-adrenergic blocking drugs, contraceptives, cardiovascular drugs,calcium channel inhibitors, depressants, diagnostics, diuretics,electrolytes, enzymes, hypnotics, hormones, hypoglycemics,hyperglycemics, muscle contractants, muscle relaxants, neoplastics,glycoproteins, nucleoproteins, DNA, RNA; lipoproteins, ophthalmics,psychic energizers, sedatives, steroids, sympathomimetics,parasympathomimetics, tranquilizers, urinary tract drugs, vaccines,vaginal drugs, vitamins, minerals, nonsteroidal anti-inflammatory drugs,angiotensin converting enzymes, polynucleotides, polypeptides,polysaccharides, and nutritional supplements.
 10. The composition ofclaim 1, wherein the agent is a hormone or a nutritional supplement. 11.The composition of claim 1, wherein the agent is a drug.
 12. Thecomposition of claim 1, wherein the agent is a polypeptide.
 13. Thecomposition of claim 1, wherein the agent is insulin, testosterone,vasopressin, interleukin-2, ACTH, angiotensin, calcitonin, vinpocetin,IGF-1, hexarelin, GHRP-6 or erythropoetin.
 14. The composition of claim1, comprising a second agent.
 15. The composition claim 14, wherein thetwo agents are testosterone and vinpocetin.
 16. The composition claim14, wherein the two agents are hexarelin and GHRP-6.
 17. The compositionof claim 2, wherein the oil phase comprises oat oil, a medium chaintriglyceride and propylene glycol.
 18. The composition claim 17, whereinthe oil is present at a concentration of about 5% by weight up to about30% by weight of the total weight of the composition.
 19. Thecomposition of claim 1, further comprising a surface active agent. 20.The composition of claim 19, wherein the surface active agent ispolysorbate-80 or phosphatidylcholine.
 21. The composition of claim 1,further comprising a cosolvent.
 22. The composition of claim 21, whereinthe cosolvent is selected from among polyhydric alcohol and combinationsof polyhydric alcohols.
 23. The composition of claim 22, wherein thecosolvent is selected from among ethylene glycol, dipropylene glycol,propylene glycol, polyethylene glycol, glycerin, butylene glycol,hexylene glycol, polyoxyethylene, polypropylene glycol, sorbitol, andmixtures thereof.
 24. The composition of claim 1, further comprising oneor more other additives selected from among taste modifying agents, abuffering agent, a chelating agent, a colorant, an osmotic modifier, apreservative, a sterilizer, a solubilizer, a tonicifier, a traceelement, and a viscomodulator.
 25. The composition claim 1 that isformulated for oral or nasal administration.
 26. A method for mucosaldelivery of an agent, comprising: contacting the composition of claim 1with a mucosal surface of a subject, whereby the agent is delivered intothe circulatory system of the subject.
 27. The method of claim 26,wherein the composition contacts a mucosal lining for a period of timethat is sufficient for quantitative delivery of the agent.
 28. Themethod of claim 27, wherein the composition adheres to or penetratesinto or adheres to and penetrates into a mucosal lining for a period oftime that is sufficient for a quantitative delivery of the agent. 29.The method of claim 28, wherein the composition adheres to andpenetrates into the mucosal lining for about 1 minute up to about 24hours.
 30. The method of claim 28, wherein the agent is selected fromamong antidiabetics, anticonvulsants, analgesics, anti-hypotensives,anti-Parkinson's drugs, anti-inflammatories, anti hypothyroid drugs,antimigraines, antinausea, calcium antagonists, anesthetics,antimicrobials, antimalarials, antiparasitics, antihypertensives,antibiotics, antihistamines, antipyretics, alpha-adrenergic agonists,alpha-blockers, biocides, bactericides, bronchial dilators,beta-adrenergic blocking drugs, contraceptives, chemotherapeutics,cardiovascular drugs, calcium channel inhibitors, depressants,glucocorticoids, mineralocorticoids, diagnostics, diuretics,electrolytes, enzymes, hypnotics, hormones, hypoglycemics,hyperglycemics, muscle contractants, muscle relaxants, neoplastics,glycoproteins, nucleoproteins, lipoproteins, ophthalmics, psychicenergizers, anti-psychotics, sedatives, steroids, sympathomimetics,parasympathomimetics, tranquilizers, urinary tract drugs, vaccines,vaginal drugs, vitamins, minerals, nonsteroidal anti-inflammatory drugs,vasodilators, angiotensin converting enzymes, polynucleotides,polypeptides, polysaccharides, nutritional and herbal supplements andcombinations thereof.
 31. A method for making the composition of claim1, comprising: dissolving components of the composition in an oil andwater phase; and mixing the two phases at a predetermined temperatureand pressure, whereby the mucoadhesive protein is associated with thedelivery vehicle.
 32. The method of claim 31, wherein the temperatureduring the dissolving and mixing step is maintained at a level thatprevents denaturation of the mucoadhesive protein.
 33. The method ofclaim 31, wherein the temperature during the dissolving and mixing stepis maintained at about 115° F. and the pressure is maintained at about25 psi.
 34. The method of claim 31, wherein the dissolving step iscarried out at about 250 rpm.
 35. A method of treating diabetescomprising: administering a composition of claim 1, to a subject,wherein the composition comprises an agent for treatment of diabetes.36. The composition of claim 1, wherein the mucoadhesive protein ispresent at a concentration of about 5% by weight up to about 50% of thetotal weight of the composition.
 37. The composition of claim 1, whereinthe mucoadhesive protein is present at a concentration of about 1% byweight up to about 11% by weight.
 38. The composition of claim 1,wherein the mucoadhesive protein is present at a concentration of atleast about 5% by weight of the total weight of the composition.
 39. Thecomposition of claim 38, wherein the mucoadhesive protein is present ata concentration of at least about 9% by weight.